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Journal articles on the topic "PHD finger"
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Wu, Qi, and Chuan Tang Wang. "Genome Wide Analysis of PHD Finger Family in Soybean (Glycine max)." Advanced Materials Research 864-867 (December 2013): 2503–8. http://dx.doi.org/10.4028/www.scientific.net/amr.864-867.2503.
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The PHD finger is a highly conserved structural domain in roles with regulating transcription and modification of chromatin structure. Forty-five PHD finger genes encoding PHD finger protein were identified from soybean (Glycine max) database. And sixty - four unique typical PHD finger domains were retrieved. NJ phylogenetic tree of all 64 PHD finger domains consisted of ten main clades (A-J). Subcellular localization analysis shows that Glyma06g33590.1, Glyma10g05080.1 and Glyma11g11720.1 may localize in Golgi body, chloroplast thylakoid membrane and mitochondrial inner membrane, respectively. The function of domain is loyal to the cause of protein situated in particular site of cell. Eight unique domains have been found concomitant with PHD domain in a certain protein. The cooperative relationship between diverse domains may important for particular biological event.
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Muntean, Andrew G., and Jay L. Hess. "The MLL PHD Fingers of MLL Block MLL Fusion Protein Mediated Transformation." Blood 110, no. 11 (2007): 976. http://dx.doi.org/10.1182/blood.v110.11.976.976.
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Abstract Mixed Lineage Leukemia (MLL) is a histone H3K4 methyltransferase that is rearranged in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). MLL is required for the maintenance of Hox gene expression. Deregulation of Hox genes by MLL fusion proteins, which fuse MLL in frame to one of over 50 different translocation partners, is critical for transformation. In these translocations, the DNMT homology (CXXC) domain is always included, but the set of adjacent plant homeodomains (PHD), which includes four PHD fingers and a bromodomain, is invariably excluded. PHD fingers have recently been described to bind tri-methylated histone H3K4 and others report PHD domains binding transcriptional co-repressors, such as Mi-2a of the NuRD complex. However, the role of the PHD fingers in MLL is not well understood. To determine the function of the PHD fingers in MLL, we performed bone marrow transduction and colony assays with the MLL fusion protein MLL-AF9, engineered to contain the PHD domain region (MLL-PHD-AF9). These experiments showed that inclusion of the PHD fingers inhibited immortalization as shown by the absence of compact colonies in methylcellulose replating assays and inhibition of proliferation in liquid cultures. Initial experiments with PHD finger deletions to map the inhibiting activity suggest inclusion of any PHD fingers beyond the first PHD finger, results in inhibition of transformation. To monitor the transcriptional activity of the retrovirally infected bone marrow cells, total RNA was isolated from cells harvested after the second replating, when significant differences were seen in colony morphology and size. Consistent with the transformation inhibition, Hoxa9 gene expression was found to be significantly repressed with respect to expression detected in transformed MLL-AF9 cells as determined by qPCR. To confirm this effect is directly due to the MLL fusion proteins, we performed luciferase assays with an MLL responsive myc E-box luciferase construct in MLL −/− MEFs. We found a specific and robust activation of the reporter in the presence of MLL-AF9, which was severely compromised by the inclusion of the PHD fingers. Together, these results suggest the PHD fingers act as transcriptional repressors that inhibit transformation. Our results provide an explanation for the finding that translocations including the coding region for C terminal PHD fingers do not occur in human leukemias and suggest that this region is also involved in the regulation of wild type MLL. We are currently studying the mechanisms of transcriptional repression mediated by the PHD fingers by isolating interacting proteins and assessing their effect on transcription and transformation.
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Soshnikova, N. V., A. A. Sheynov, Eu V. Tatarskiy, and S. G. Georgieva. "The DPF Domain As a Unique Structural Unit Participating in Transcriptional Activation, Cell Differentiation, and Malignant Transformation." Acta Naturae 12, no. 4 (2020): 57–65. http://dx.doi.org/10.32607/actanaturae.11092.
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The DPF (double PHD finger) domain consists of two PHD fingers organized in tandem. The two PHD-finger domains within a DPF form a single structure that interacts with the modification of the N-terminal histone fragment in a way different from that for single PHD fingers. Several histone modifications interacting with the DPF domain have already been identified. They include acetylation of H3K14 and H3K9, as well as crotonylation of H3K14. These modifications are found predominantly in transcriptionally active chromatin. Proteins containing DPF belong to two classes of protein complexes, which are the transcriptional coactivators involved in the regulation of the chromatin structure. These are the histone acetyltransferase complex belonging to the MYST family and the SWI/SNF chromatin-remodeling complex. The DPF domain is responsible for the specificity of the interactions between these complexes and chromatin. Proteins containing DPF play a crucial role in the activation of the transcription of a number of genes expressed during the development of an organism. These genes are important in the differentiation and malignant transformation of mammalian cells.
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Boamah, Daniel, Tao Lin, Franchesca A. Poppinga, et al. "Characteristics of a PHD Finger Subtype." Biochemistry 57, no. 5 (2018): 525–39. http://dx.doi.org/10.1021/acs.biochem.7b00705.
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He, Chao, Ning Liu, Dongya Xie, Yanhong Liu, Yazhong Xiao, and Fudong Li. "Structural basis for histone H3K4me3 recognition by the N-terminal domain of the PHD finger protein Spp1." Biochemical Journal 476, no. 13 (2019): 1957–73. http://dx.doi.org/10.1042/bcj20190091.
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Abstract Saccharomyces cerevisiae Spp1, a plant homeodomain (PHD) finger containing protein, is a critical subunit of the histone H3K4 methyltransferase complex of proteins associated with Set1 (COMPASS). The chromatin binding affinity of the PHD finger of Spp1 has been proposed to modulate COMPASS activity. During meiosis, Spp1 plays another role in promoting programmed double-strand break (DSB) formation by binding H3K4me3 via its PHD finger and interacting with a DSB protein, Mer2. However, how the Spp1 PHD finger performs site-specific readout of H3K4me3 is still not fully understood. In the present study, we determined the crystal structure of the highly conserved Spp1 N-terminal domain (Sc_Spp1NTD) in complex with the H3K4me3 peptide. The structure shows that Sc_Spp1NTD comprises a PHD finger responsible for methylated H3K4 recognition and a C3H-type zinc finger necessary to ensure the overall structural stability. Our isothermal titration calorimetry results show that binding of H3K4me3 to Sc_Spp1NTD is mildly inhibited by H3R2 methylation, weakened by H3T6 phosphorylation, and abrogated by H3T3 phosphorylation. This histone modification cross-talk, which is conserved in the Saccharomyces pombe and mammalian orthologs of Sc_Spp1 in vitro, can be rationalized structurally and might contribute to the roles of Spp1 in COMPASS activity regulation and meiotic recombination.
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Kalkhoven, Eric, Hans Teunissen, Ada Houweling, C. Peter Verrijzer, and Alt Zantema. "The PHD Type Zinc Finger Is an Integral Part of the CBP Acetyltransferase Domain." Molecular and Cellular Biology 22, no. 7 (2002): 1961–70. http://dx.doi.org/10.1128/mcb.22.7.1961-1970.2002.
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ABSTRACT Histone acetyltransferases (HATs) such as CBP and p300 are regarded as key regulators of RNA polymerase II-mediated transcription, but the critical structural features of their HAT modules remain ill defined. The HAT domains of CBP and p300 are characterized by the presence of a highly conserved putative plant homeodomain (PHD) (C4HC3) type zinc finger, which is part of the functionally uncharacterized cysteine-histidine-rich region 2 (CH2). Here we show that this region conforms to the PHD type zinc finger consensus and that it is essential for in vitro acetylation of core histones and the basal transcription factor TFIIE34 as well as for CBP autoacetylation. PHD finger mutations also reduced the transcriptional activity of the full-length CBP protein when tested on transfected reporter genes. Importantly, similar results were obtained on integrated reporters, which reflect a more natural chromatinized state. Taken together, our results indicate that the PHD finger forms an integral part of the enzymatic core of the HAT domain of CBP.
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May, Meiling, Stephen Desiderio, and John Thomas Bettridge. "An Allosteric Mechanism for Epigenetic Activation of the V(D)J Recombinase." Blood 132, Supplement 1 (2018): 512. http://dx.doi.org/10.1182/blood-2018-99-116675.
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Abstract V(D)J recombination, the process by which antigen receptor genes are assembled from discrete DNA segments during lymphoid development, is responsible for the generation of the primary immune repertoire. Errors in V(D)J recombination have been implicated in the pathogenesis of lymphoid malignancies, including follicular lymphoma, MALT lymphoma and mantle cell lymphoma. V(D)J recombination is initiated by a specialized transposase, RAG, consisting of RAG-1 and RAG-2 subunits. RAG mobilizes participating gene segments in a site-specific fashion by cleaving DNA at conserved recombination signal sequences. The accessibility of these sequences to RAG is subject to locus- and developmental stage-specific control by mechanisms that are as yet poorly understood. Elucidation of these mechanisms is fundamental to our understanding of the off-target events linking RAG activity to tumorigenesis. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). RAG-2 contains a plant homeodomain (PHD) finger that binds specifically to H3K4me3. Disruption of this PHD finger impairs V(D)J recombination in vivo. Peptides bearing H3K4me3 stimulate substrate binding and catalysis of DNA cleavage by RAG. This stimulation is dependent on an intact PHD finger, suggesting that H3K4me3 is an allosteric activator of the V(D)J recombinase. Indeed, binding of H3K4me3 to the RAG-2 PHD induces dynamic conformational changes in RAG-1. Because substrate binding and catalysis are functions of RAG-1, information regarding occupancy of the RAG-2 PHD must be transmitted to the RAG-1 subunit. To understand how the recognition of active chromatin is coupled to the binding and cleavage of recombination signal sequences, we sought to trace the path of allostery from the RAG-2 PHD finger to RAG-1. Our strategy has been: (1) to generate chimeric RAG-2 proteins in which the mouse PHD finger is replaced by the PHD finger of a phylogenetically distant RAG-2; (2) to identify chimeric RAG-2 proteins that are capable of binding H3K4me3 but incapable of allosteric activation; (3) to systematically back-mutate residues in the foreign PHD to the mouse sequence; and (4) to identify back-mutations that rescue allosteric activation. A chimeric RAG-2 protein in which the mouse PHD finger is replaced by the corresponding domain from the bamboo shark, C. punctatum, fails to support V(D)J recombination in vivo. This chimeric protein retains the ability to bind H3K4me3 but engagement of H3K4me3 does not result in allosteric activation, suggesting that the allosteric interface of the PHD finger is disrupted. The amino acid sequence differences between mouse and C. punctatum form several clusters, located on the opposite side of the PHD from the H3K4me3 binding site. Each of these clusters in the C. punctatum PHD finger was mutated to the mouse sequence and the corresponding back-mutated chimeric RAG-2 proteins were tested for their ability to support V(D)J recombination. Strikingly, mutation of one such cluster, corresponding to residues 425 - 429, 431 and 433 of mouse RAG-2, was sufficient to rescue recombination activity to the level of wild-type. Taken together, our observations indicate that the binding of H3K4me3 by RAG-2 is itself insufficient to support recombination; rather, information regarding the engagement of H3K4me3 must be transmitted allosterically. Moreover, our mutational analysis has identified a putative allosteric surface within the PHD finger and distinct from the H3K4me3 binding site that is responsible for transmitting the allosteric signal. The requirement for allosteric activation by H3K4me3 may play a role in defining patterns of RAG-mediated DNA cleavage during normal development and in the generation of lymphoid malignancies. Disclosures Desiderio: Genentech: Consultancy; AbbVie: Consultancy.
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May, Meiling R., John T. Bettridge, and Stephen Desiderio. "Binding and allosteric transmission of histone H3 Lys-4 trimethylation to the recombinase RAG-1 are separable functions of the RAG-2 plant homeodomain finger." Journal of Biological Chemistry 295, no. 27 (2020): 9052–60. http://dx.doi.org/10.1074/jbc.ra120.014382.
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V(D)J recombination is initiated by the recombination-activating gene protein (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with gene transcription and with epigenetic marks characteristic of active chromatin, including histone H3 trimethylated at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 induces conformational changes in RAG-1, allosterically stimulating substrate binding and catalysis. To better understand the path of allostery from the RAG-2 PHD finger to RAG-1, here we employed phylogenetic substitution. We observed that a chimeric RAG-2 protein in which the mouse PHD finger is replaced by the corresponding domain from the shark Chiloscyllium punctatum binds H3K4me3 but fails to transmit an allosteric signal, indicating that binding of H3K4me3 by RAG-2 is insufficient to support recombination. By substituting residues in the C. punctatum PHD with the corresponding residues in the mouse PHD and testing for rescue of allostery, we demonstrate that H3K4me3 binding and transmission of an allosteric signal to RAG-1 are separable functions of the RAG-2 PHD finger.
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Musselman, Catherine A., and Tatiana G. Kutateladze. "The PHD finger of Spp1 mediates histone modification cross-talk." Biochemical Journal 476, no. 16 (2019): 2351–54. http://dx.doi.org/10.1042/bcj20190492.
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Abstract Binding of the Spp1 PHD finger to histone H3K4me3 is sensitive to adjacent post-translational modifications in the histone tail. This commentary discusses the findings of He and colleagues [Biochem. J.476, 1957–1973] which show that the PHD finger binds to H3K4me3 in a selective manner which is conserved in the Saccharomyces pombe and mammalian orthologues of Spp1.
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Bortoluzzi, Alessio, Anastasia Amato, Xavier Lucas, Manuel Blank, and Alessio Ciulli. "Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains." Biochemical Journal 474, no. 10 (2017): 1633–51. http://dx.doi.org/10.1042/bcj20161053.
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The plant homeodomain (PHD) fingers are among the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation; however, less is known about the recognition of secondary structure features within the histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A [BAZ2A, also known as TIP5 (TTF-I/interacting protein 5)] in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name ‘acidic wall’, found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or destabilization of H3 helicity. Our work unravels the structural basis for binding of the helical H3 tail by PHD fingers and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes.
Dissertations / Theses on the topic "PHD finger"
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Deeves, Sian Elizabeth. "Novel functions of the MOZ double PHD finger domain." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12503/.
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Monocytic leukaemia zinc-finger protein (MOZ) is a histone acetyltransferase (HAT) implicated in haematopoiesis and acute myeloid leukaemia, as well as embryonic and postnatal development. MOZ contains multiple domains, including a MYST HAT domain and a double PHD finger domain (DPF) suggesting it interacts with histones. This work has established for the first time that the MOZ DPF exhibits dual functionality in establishing and sensing post-translational modifications (PTMs) of histones. Firstly, our data detected the direct interaction of MOZ with the N-terminal tails of histones H3 and H4 and shows that the MOZ DPF domain mediates such binding. Both PHD fingers are required and functionally cooperate to establish the DPF histone binding preference in terms of PTMs. We demonstrate that H3K4me3 prevents MOZ DPF association with H3, although H3K4me2 is tolerated. Similarly, H4Kac acts as a dominant exit signal that excludes MOZ from chromatin. This ability to sense H3K4 PTM status was confirmed in a collaborative effort establishing the crystal structure of MOZ DPF in complex with an unmodified H3 peptide. The H3 peptide adopted an α-helical conformation in the complex, which has not previously been observed. Secondly, we present novel data showing that the MOZ DPF domain exhibits a mild histone H3-specific acetyltransferase activity. This provides the first report of a possible enzymatic role in chromatin modification attributed to a PHD finger. Furthermore, the combined DPF and MYST domains were found to influence the reaction rate and substrate specificity of MOZ-induced histone acetylation. Our studies revealed that the MOZ DPF could associate with heterochromatic PTMs, namely H3K9me3. We report here that both the H3K9-specific methyltransferase SUV39H1 and heterochromatin protein 1 (HP1) form interactions with MOZ, implicating its function in both corepressor and coactivator complexes. Thus, our data suggest that like several other chromatin-associated proteins, MOZ is a multi-functional regulator of chromatin modification and gene expression.
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ZUCCHELLI, CHIARA. "THE PHD FINGER OF SP140: A STRUCTURAL AND FUNCTIONAL STUDY." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/148885.
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Sp140 is an IFNg-inducible leukocyte-specific member of the Sp100 family proteins. Along with the PML tumor suppressor, Sp100 family proteins are major components of PML-nuclear bodies (PML-NBs), they interact with DNA and various regulatory factors and may be involved in chromatin-dependent transcriptional activation or repression. Sp140 is expressed in all human mature B cells and plasma cell lines, as well as some T cells, suggesting an important role in cellular functions that are peculiar to these cells. In mammalian cells Sp140 behaves as a transcription co-activator for a reporter gene (Bloch et al, 2000). Despite the involvement in B-cell Chronic Lymphocytic Leukaemia (CLL, OMIM151400) (Di Bernardo et al, 2008) and HIV-1 replication (Guldner et al, 1992), until now Sp140 physiological and pathological role is unknown and unexplored, both at cellular and molecular level.
The predicted Sp140 amino acid sequence, 867 residues in length, indicates a modular structure similar to other Sp100 family members (Bloch et al, 1996). The N-terminus HSR domain (amino acids 36-157) is responsible both for PML-NBs targeting and homo/hetero-dimerization. The region between residues 306-404 is strongly negatively charged, while the central portion contains a putative bipartite nuclear localization signal, a SAND domain (residues 588-661), a PHD finger (residues 692-734) and a bromodomain (residues 756-859). In this thesis we investigated Sp140 PHD finger both at functional and structural level.
Structural determination was performed in solution by means of NMR spectroscopy. Analysis of 1H-15N HSQC spectra of Sp140 15N PHD finger wild type and 15N PHD finger P45A mutant revealed peptidyl-prolyl cis trans isomerization of the T44-P45 peptide bond and a ratio between cis and trans conformers of 1:2. As the NetPhos 2.0 server predicts phosphorylation of the T44 residue by the p38 mitogen-activated protein kinase (p38 MAPK), we suppose that the phosphorylated T44-P45 bond might be a site of regulation of the domain structure through the activity of PIN-1, an enzyme that efficiently and specifically bind to and isomerizes the phosphorylated S/T-P motifs in proteins (Wulf et al, 2005).
Using triple resonance NMR experiments we assigned 95% of backbone resonances, 96% of side chain 1H resonances and 73% of side chain non-1H resonances (side chain resonances of OH, SH, CO, NH and NH2 groups were not assigned) of the Sp140 PHD finger trans conformer. The tautomeric state of the two histidines was determined, analyzing a 1H-15N long range correlation HSQC spectrum. The 3J(HNHa) coupling constants and the corresponding phi dihedral angles were calculated by analysis of the 3D HNHA spectrum and were then compared to those predicted by TALOS+ software. We manually assigned more than 850 NOE cross-peaks of the 2D and 3D NOESY spectra. NOEs restraints and 12 dihedral angles were employed for structure calculation of the Sp140 trans conformer by means of ARIA 2.1.3 software. The best NMR ensemble achieved up to now showed a compact globular fold with two short a-helices (stretches 12-EVCR-15 and 50-FCRM-53) as the sole elements of secondary structure. Analysis of the electrostatic surface potential revealed the strong negative charged character of the Sp140 PHD finger trans conformer, with a positive patch only on one side of the domain.
Heteronuclear NOE experiments revealed that loop 2, containing the T44-P45 bond which undergoes cis trans isomerization is flexible from E40 to N47. Also the N-terminal tail of the domain is flexible up to residue L8. Flexibility caused a limited number of available NOE restraints in these two regions, especially in loop 2, and consequently an overall high backbone RMSD of the NMR ensemble. In order to increase the number of NOE restraints to calculate the structure we have recently acquired NOESY spectra at higher magnetic fields (900 MHz 1H frequency) that will be soon analyzed.
We next investigated the functional role of Sp140 PHD finger and verified its ability to work as histone binding modules. According to sequence alignments, Sp140 PHD finger belongs to the PHD finger subclass specifically recognizing the H3K4me0 epigenetic mark. Indeed, it has an N-terminal conserved aspartic acid which should be involved in electrostatic interactions with the unmodified histone K4 side-chain, as previously demonstrated by both AIRE PHD1 (Chignola et al, 2009) and BHC80 PHD finger (Lan et al, 2007) structures in complex with an unmodified H3 peptide. Unexpectedly tryptophan fluorescence and NMR titrations of Sp140 PHD finger with a 15mer H3K4me0 peptide showed no binding, indicating that the presence of the N-terminal acidic hallmark is not sufficient to predict binding to the H3K4me0 epigenetic mark. We next explored the possibility that SP140 PHD finger might recognize other epigenetic modifications, we therefore extended our binding assays to other synthetic peptides carrying different types of epigenetic marks (such as methylation or acetylation). We also applied a large screening approach using the MODifiedTM Histone Peptide Arrays, which allows the screening of 384 unique modification combinations on the N-terminal tails of histone H3 (up to residue 45), H4 (up to residue 30), H2A and H2B (up to residue 19). However, until now we identified no specific binding of Sp140 PHD finger to the unmodified histone tails and to any combination of histone epigenetic marks spotted on the array (acetylation, methylation, phosphorylation and citrullination).
Taken together these data suggest that Sp140 PHD finger is not a classical epigenetic reader and other functions might be attributed to this domain, such as a SUMO E3 ligase activity towards the adjacent bromodomain. This hypothesis was supported by the presence of a typical KxE SUMOylation site at the N-terminus of the Sp140 bromodomain (761-LKCE-764) and by recent data on KAP1 PHD finger, which functions as SUMO E3 ligase for the adjacent bromodomain (Ivanov et al, 2007; Zeng et al, 2008). In support to this hypothesis NMR titration experiments revealed binding of recombinant SUMO E2 ligase Ubc9 to a small, well defined surface of Sp140 PHD finger. We next expressed and purified in E.coli Sp140 PHD finger – bromodomain (PB) tandem and through in vitro SUMOylation test and mass spectrometry analysis we found that the construct was SUMOylated on lysine K837. This residue constitutes an atypical SUMOylation site, located at the bromodomain BC loop. Importantly, sequence alignment reveals that this position corresponds to one of the four SUMOylation sites indentified in KAP1 bromodomain. The intramolecular SUMO E3 ligase activity of Sp140 PHD finger is also supported by the observation that Sp140 PHD finger and bromodomain interact with each other, as deduced by superposition of the 1H-15N HSQC spectra of Sp140 PHD finger alone and PB tandem. Interaction could occur through the hydrophobic core made by stretch 765-FLLLKV-770 in the bromodomain and V695, F712, F718, F732 residues in the PHD finger. Indeed, this is the same core that mediates KAP1 PHD finger and bromodomain interaction, leading to a structural and functional unit whose integrity is fundamental for the KAP1 PHD finger SUMO E3 liagse activity (Zeng et al, 2008). Through NMR titrations we also demonstrated binding of SUMO-1 to both Sp140 PHD finger alone and PB tandem. The binding surface mapped on the homology model of the PB tandem is in agreement with the covalent addition of one SUMO-1 moiety to both the bromodomain K873 and K762 (in the typical KxE SUMOylation site at the bromodomain N-terminus). We are currently performing mutagenesis experiments to confirm the two Sp140 PB tandem SUMOylation sites by means of in vitro SUMOylation tests and mass spectrometry analysis on the Sp140 PB tandem single mutants K762R and K837R. To further validate the intramolecular SUMO E3 ligase activity of the PHD finger we will perform in vitro SUMOylation tests on a PB tandem mutant, in which the function of the PHD finger is inhibited trough an unfolding mutation.
In this thesis we have collected strong evidences that in vitro Sp140 PHD finger has SUMO E3 ligase activity for the adjacent bromodomain. This finding might have an important biological relevance in the context of the full length protein: first of all the SUMO E3 ligase activity correlates well with Sp140 localization in leukocytes PML-NBs. PML-NBs are nuclear sub-compartments in which 48% of their protein components show one or more SUMOylation sites which, once they are SUMOylated, work as PML-NBs recruitment signal for these proteins (Van Damme et al, 2010). A similar mechanism could be hypothesized for Sp140 protein, whereby the PHD finger mediates the SUMOylation of the adjacent bromodomain in order to enable the protein recruitment to PML-NBs. SUMOylation might also have a role in the Sp140 transcription co-activating function, other than localization. It is conceivable that Sp140 SUMOylation might recruit proteins able to interact non-covalently with the conjugated SUMO-1 through their SIMs (SUMO Interaction Motifs). Hereby SUMOylated Sp140 protein might serve as a platform for the assembly of a leukocyte-specific transcription complex, whose target genes are still to be identified. Importantly, a similar mechanism has been observed for the co-repressor KAP1; SUMOylation is required for KAP1-mediated gene silencing, because the SUMOylated bromodomain serves as a scaffold and recruits the SETDB1 histone methyltransferase and the CHD3/Mi2 component of the NuRD complex through recognition of the SUMO moieties by the SIMs of these proteins (Ivanov et al, 2007).
Through NMR and ITC titrations we found that Sp140 PB tandem is able to bind to a 15mer H3K9ac synthetic peptide. We excluded any PHD finger involvement in this interaction, because when we titrated the H3K9ac peptide to Sp140 PHD finger alone we did not see any binding. Therefore Sp140 bromodomain seems to retain the characteristic ability of bromodomains to bind to acetylated histone tails, despite it does not show the conserved Tyr, Tyr and Asn residues employed by bromodomains in order to bind to acetylated lysines. If confirmed, these results suggest that Sp140 bromodomain is characterized by a new, peculiar mode of recognition of acetylated histone tails.
In conclusion, we are collecting important functional and structural data on two domains (PHD finger and bromodomain) of Sp140, a leukocyte-specific nuclear protein involved in B-cell Chronic Lymphocytic Leukaemia and HIV-1 replication, but unexplored up to now. Our functional data strongly indicate that the two domains interact with each other constituting a structural and functional unit in which the PHD finger mediates SUMOylation of the bromodomain. We are solving the NMR solution structure of the Sp140 PHD finger trans conformer. With the exception of the T44-P45 peptidyl-prolyl cis trans isomerization, we are not observing great differences with the solved structures of PHD fingers recognizing histone H3 epigenetic marks, on the contrary of Sp140 PHD finger. Therefore, our data further support the concept that PHD fingers are versatile domains able to perform different activities according subtle but significant structural differences.
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Berardi, A. "STRUCTURAL INSIGHTS INTO THE INTERACTION BETWEEN THE TANDEM PHD FINGER DOMAIN P5C5 OF NSD1 AND THE ZINC FINGER MOTIF C2HR OF NIZP1." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/247139.
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Point Mutations or translocation in NSD1 cause the overgrowth disorder Sotos syndrome and acute myeloid leukemia (AML), respectively (Berdasco M. et al, 2009, Wang G et al, 2003). NSD1 contains several chromatin related domains including a SET domain responsible for histone methyltranferases activity (H3K36 and H4K20), two nuclear receptor-interaction (NID) motifs, five zinc finger domains (PHD1-5), a variant PHD finger (C5HCH), two proline-tryptophan-proline-tryptophan (PWWP1-2) domains (Lucio-Eterovic AK, et al , 2011), suggesting a role in chromatin regulation and gene expression. 20 pathological Sotos mutations have been detected on the PHD tandem domain composed by NSD1-PHD5 and NSD1-C5HCH (NSD1-P5C5). The tandem domain is essential for the pathogenesis of acute myeloid leukaemia (AML) caused by the chimeric protein NUP98/NSD1 that forces the abnormal activation of Hox-A and Meis1 genes (Wang at al 2007). The deletion of this tandem domain is sufficient to abolish NUP98/NSD1 interaction with chromatin, preventing both the transcription activation of HOX genes and the immortalization of myeloid progenitors. The biological role of NSD1-P5C5 is still unclear. It was proposed that this tandem domain is involved in the recognition of both H3K4me3 and H3K9me3 histone marks, (Pasillas M et al. 2011). However, biophysical experiments in our laboratory did not confirm these results challenging the idea that this tandem domain can really work as epigenetic reader. Previous biochemical studies suggested that NSD1-P5C5 can also work as protein-protein interaction motif, being able to bind to the co-repressor Nizp1 by its C2HR zinc fingers motif (Nizp1-C2HR) thus mediating gene repression (Nielsen AL et al, 2004).
The structural determinants of this interaction are still unknown and have been object of this thesis. In order to get more insights into the physiological and pathological role of NSD1-P5C5, we have solved its (i) solution structure by NMR spectroscopy and (ii) characterized its interaction with Nizp1-C2HR.
NSD1-P5C5 folds as unique functional unit adopting a “face to side orientation”. In particular NSD1-PHD5 (or NSD1-P5) presents the canonical PHD finger fold, whereas the NSD1-C5HCH (or NSD1-C5) domain displays an atypical topology characterized by the presence of an additional two stranded β-sheet. In order to investigate the impact of Sotos point mutation on NSD1-P5C5 we expressed and purified seven mutants and analyzed them by NMR. The majority of them destabilize the fold, with the exception of the solvent exposed mutation Arg2152Gln and His2205Arg suggesting a functional role for these residues.
We next solved the solution structure of the zinc finger Nizp1-C2HR, an atypical Cys2His2-type zinc finger in which the fourth zinc chelating residue is substituted by an arginine residue. Its fold consists of a short α-helix and of a short two-stranded β-sheet hold together by one zinc ion. Importantly, we showed that three zinc ligands are sufficient to maintain the protein domain fold and functionality.
NMR titrations of 15N labelled NSD1-P5C5 with Nizp1-C2HR and 15N labelled Nizp1-C2HR with NSD1-P5C5 clearly show that the two proteins directly interact. Analysis of the chemical shift displacements upon complex formation allowed to identify the residues of the two protein domains involved in protein-protein interaction. The interaction surface is located on the interface between NSD1-P5 and NSD1-C5 and on the α-helix of Nizp1-C2HR, respectively.
Based on this information using the software HADDOCK we have computed a data driven docking model of the protein complex. In the model Nizp1-C2HR places its α-helix in the groove at the interface between NSD1-P5 and NSD1-C5, creating both hydrophobic and polar intermolecular contacts.
The thermodynamic parameters that govern complex formation were studied by ITC titrations: the binding reaction is entropy-driven, with a stoichiometry of 1:1 and a Kd of 3,80±0,66 μM. In order to solve the structure of the protein complex we performed crystallographic screenings, and we have found preliminary conditions for obtaining single crystals.
In conclusion, the presented results provide novel information on the interaction between a tandem PHD finger domain and zinc finger motif. The results represent, to the best of our knowledge, the first biophysical characterization between two zinc binding domains. Most importantly, these data give the first molecular details of the interaction between NSD1 and Nizp1 and may provide useful insights into the function of NSD1 and its role in pathological conditions both in Sotos Syndrome and AML. Future work will be dedicated to the full three-dimensional characterization of the complex and to the analysis of Sotos mutations on complex formation.
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Amato, Anastasia. "Structural studies of paired PHD finger-bromodomain chromatin-binding modules : targeting epigenetic readers with chemical probes." Thesis, University of Dundee, 2018. https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b.
Full textAbstract:
The use of chemical probes is a powerful tool that can help to address important biological questions. The study presented in this thesis aims to target reader domains of chromatin-associated proteins with small molecules, in order to provide information on their ligandability, useful to develop - potent chemical probes. This thesis work is divided in three parts. In the first and second part it is shown how structural information obtained by the use of synthetic peptides to study the binding mode of reader domains with their natural binding partner can be combined with fragment screening to gauge future optimization of small molecules. The first section described the disclosure of the binding mode of the H3 histone tail by the PHD zinc finger of BAZ2A. A crystal structure of the complex of BAZ2A with the H3 10-mer peptide identified a helical conformation of H3 upon binding with the PHD. This information coupled with further structural and biophysical analysis led to the identification of a subfamily of PHD characterized by an acidic patch on the helical turn, which is responsible of inducing helicity on H3 tail upon binding. The second part of the work investigated the ligandability of the PHD zinc finger domains of BAZ2A and BAZ2B. Using a combination of biophysical techniques and X-ray crystallography it was probed that it is possible to target these reader domains. Despite the similarities of the two PHDs, comparison of the fragment-bound crystal structures of the two proteins highlighted some differences in the binding mode. The last part of the project describes the several attempts performed in trying to elucidate the histone binding partner of the PHD-BrD tandem of the chromatin-related proteins BAZ1B and TRIM66, both involved in diseases.
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Mack, Marissa. "Investigation into the Specification of NURF Recruitment to the Genome." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3843.
Full textAbstract:
The nucleosome remodeling factor (NURF) is a mutli-protein complex that plays a role in the regulation of gene expression through its ability to remodel nucleosomes. The largest subunit of this complex, Bptf (Bromodomain PHD Finger Transcription Factor) is important for many cellular processes as a transcriptional regulator and improper function results in disease or malignancy. To further understand the genome-wide recruitment of the NURF complex, the interaction partner for the N-terminal PHD finger domain of Bptf was investigated through pull down assays followed by mass spectrometry. It was determined that this domain does not recognize histones; instead it recognizes a nonhistone protein, Thoc4 or Hmgb1. The expression of a cDNA corresponding to Bptf was also tested for expression in mouse ES cells after the addition of two exons found to be missing in the original cDNA. Addition of this sequence did not allow for exogenous Bptf expression in ES cells.
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Mitra, Sayantan. "Arabidopsis Cohesin proteins: WAPL, CTF7 and PHD finger proteins: MMDL1, MMDL2 are essential for proper meiosis, gamete development and plant growth." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1517605898967702.
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Dzidek, Brygida Maria. "Tribological interactions of the finger pad and tactile displays." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7909/.
Full textAbstract:
This thesis summarise the results of an investigation of the tribological interactions of the human finger pad with different surfaces and tactile displays. In the wide range of analyses of the mechanical properties of the finger pad, an attempt has been made to explain the nature of the interactions based on critical material parameters and experimental data. The experimental data are presented together with detailed modelling of the contact mechanics of the finger pad compressed against a smooth flat surface. Based on the model and the experimental data, it was possible to account of the loading behaviour of a finger pad and derive the Young’s modulus of the fingerprint ridges. The frictional measurements of a finger pad against smooth flat surfaces are consistent with an occlusion mechanism that is governed by first order kinetics. In contrast, measurements against a rough surface demonstrated that the friction is unaffected by occlusion since Coulombic slip was exhibited. The thesis includes an investigation of critical parameters such as the contact area. It has been shown that four characteristic length scales, rather than just two as previously assumed, are required to describe the contact mechanics of the finger pad. In addition, there are two characteristic times respectively associated with the growth rates of junctions formed by the finger pad ridges and of the real area of contact. These length and time scales are important in understanding how the Archardian-Hertzian transition drives both the large increase of friction and the reduction of the areal load index during persisting finger contacts with impermeable surfaces. Established and novel models were evaluated with statistically meaningful experiments for phenomena such as lateral displacement, electrostatic forces and squeeze-film that have advanced applications.
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Kwan, Ann Hau Yu. "Protein Design Based on a PHD Scaffold." Thesis, The University of Sydney, 2004. http://hdl.handle.net/2123/564.
Full textAbstract:
The plant homeodomain (PHD) is a protein domain of ~45�100 residues characterised by a Cys4-His-Cys3 zinc-binding motif. When we commenced our study of the PHD in 2000, it was clear that the domain was commonly found in proteins involved in transcription. Sequence alignments indicate that while the cysteines, histidine and a few other key residues are strictly conserved, the rest of the domain varies greatly in terms of both amino acid composition and length. However, no structural information was available on the PHD and little was known about its function. We were therefore interested in determining the structure of a PHD in the hope that this might shed some light on its function and molecular mechanism of action. Our work began with the structure determination of a representative PHD, Mi2b-P2, and this work is presented in Chapter 3. Through comparison of this structure with the two other PHD structures that were determined during the course of our work, it became clear that PHDs adopt a well-defined globular fold with a superimposable core region. In addition, PHDs contain two loop regions (termed L1 and L3) that display increased flexibility and overlay less well between the three PHD structures available. These L1 and L3 regions correspond to variable regions identified earlier in PHD sequence alignments, indicating that L1 and L3 are probably not crucial for the PHD fold, but are instead likely to be responsible for imparting function(s) to the PHD. Indeed, numerous recent functional studies of PHDs from different proteins have since demonstrated their ability in binding a range of other proteins. In order to ascertain whether or not L1 and L3 were in fact dispensable for folding, we made extensive mutations (including both insertions and substitutions) in the loop regions of Mi2b-P2 and showed that the structure was maintained. We then went on to illustrate that a new function could be imparted to Mi2b-P2 by inserting a five-residue CtBP-binding motif into the L1 region and showed this chimera could fold and bind CtBP. Having established that the PHD could adopt a new binding function, we next sought to use combinatorial methods to introduce other novel functions into the PHD scaffold. Phage display was selected for this purpose, because it is a well-established technique and has been used successfully to engineer zinc-binding domains by other researchers. However, in order to establish this technique in our laboratory, we first chose a control system in which two partner proteins were already known to interact in vitro. We chose the protein complex formed between the transcriptional regulators LMO2 and ldb1 as a test case. We have examined this interaction in detail in our laboratory, and determined its three-dimensional structure. Furthermore, inappropriate formation of this complex is implicated in the onset of T-cell acute lymphoblastic leukemia. We therefore sought to use phage display to engineer ldb1 mimics that could potentially compete against wild-type ldb1 for LMO2, and this work is described in Chapter 4. Using a phage library containing ~3 x 10 7 variants of the LMO2-binding region of ldb1, we isolated mutants that were able to interact with LMO2 with higher affinity and specificity than wild-type ldb1. These ldb1 mutants represent a first step towards finding potential therapeutics for treating LMO-associated diseases. Having established phage display in our laboratory, we went on to search for PHD mutants that could bind selected target proteins. This work is described in Chapter 5. We created three PHD libraries with eight randomized residues in each of L1, L3 or in both loops of the PHD. These PHD libraries were then screened against four target proteins. After four rounds of selection, we were able to isolate a PHD mutant (dubbed L13-FH6) that could bind our test protein Fli-ets. This result demonstrates that a novel function can be imparted to the PHD using combinatorial methods and opens the way for further work in applying the PHD scaffold to other protein design work. In summary, the work detailed in Chapters 3 and 5 demonstrates that the PHD possesses many of the properties that are desirable for a protein scaffold for molecular recognition, including small size, stability, and a well-characterised structure. Moreover, the PHD motif possesses two loops (L1 and L3) of substantial size that can be remodeled for target binding. This may lead to an enhancement of binding affinities and specificities over other small scaffolds that have only one variable loop. In light of the fact that PHDs are mainly found in nuclear proteins, it is reasonable to expect that engineered PHDs could be expressed and function in an intracellular environment, unlike many other scaffolds that can only function in an oxidizing environment. Therefore, our results together with other currently available genomic and functional information indicate PHD is an excellent candidate for a scaffold that could be used to modify cellular processes. Appendices 1 and 2 describe completed bodies of work on unrelated projects that I have carried out during the course of my PhD candidature. The first comprises the invention and application of DNA sequences that contain all N-base sequences in the minimum possible length. This work is presented as a reprint of our recently published paper in Nucleic Acids Research. The second Appendix describes our structural analysis of an antifreeze protein from the shorthorn sculpin, a fish that lives in the Arctic and Antarctic oceans. This work is presented as a manuscript that is currently under review at the Journal of the American Chemical Society.
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Kwan, Ann Hau Yu. "Protein Design Based on a PHD Scaffold." University of Sydney. Molecular and Microbial Biosciences, 2004. http://hdl.handle.net/2123/564.
Full textAbstract:
The plant homeodomain (PHD) is a protein domain of ~45�100 residues characterised by a Cys4-His-Cys3 zinc-binding motif. When we commenced our study of the PHD in 2000, it was clear that the domain was commonly found in proteins involved in transcription. Sequence alignments indicate that while the cysteines, histidine and a few other key residues are strictly conserved, the rest of the domain varies greatly in terms of both amino acid composition and length. However, no structural information was available on the PHD and little was known about its function. We were therefore interested in determining the structure of a PHD in the hope that this might shed some light on its function and molecular mechanism of action. Our work began with the structure determination of a representative PHD, Mi2b-P2, and this work is presented in Chapter 3. Through comparison of this structure with the two other PHD structures that were determined during the course of our work, it became clear that PHDs adopt a well-defined globular fold with a superimposable core region. In addition, PHDs contain two loop regions (termed L1 and L3) that display increased flexibility and overlay less well between the three PHD structures available. These L1 and L3 regions correspond to variable regions identified earlier in PHD sequence alignments, indicating that L1 and L3 are probably not crucial for the PHD fold, but are instead likely to be responsible for imparting function(s) to the PHD. Indeed, numerous recent functional studies of PHDs from different proteins have since demonstrated their ability in binding a range of other proteins. In order to ascertain whether or not L1 and L3 were in fact dispensable for folding, we made extensive mutations (including both insertions and substitutions) in the loop regions of Mi2b-P2 and showed that the structure was maintained. We then went on to illustrate that a new function could be imparted to Mi2b-P2 by inserting a five-residue CtBP-binding motif into the L1 region and showed this chimera could fold and bind CtBP. Having established that the PHD could adopt a new binding function, we next sought to use combinatorial methods to introduce other novel functions into the PHD scaffold. Phage display was selected for this purpose, because it is a well-established technique and has been used successfully to engineer zinc-binding domains by other researchers. However, in order to establish this technique in our laboratory, we first chose a control system in which two partner proteins were already known to interact in vitro. We chose the protein complex formed between the transcriptional regulators LMO2 and ldb1 as a test case. We have examined this interaction in detail in our laboratory, and determined its three-dimensional structure. Furthermore, inappropriate formation of this complex is implicated in the onset of T-cell acute lymphoblastic leukemia. We therefore sought to use phage display to engineer ldb1 mimics that could potentially compete against wild-type ldb1 for LMO2, and this work is described in Chapter 4. Using a phage library containing ~3 x 10 7 variants of the LMO2-binding region of ldb1, we isolated mutants that were able to interact with LMO2 with higher affinity and specificity than wild-type ldb1. These ldb1 mutants represent a first step towards finding potential therapeutics for treating LMO-associated diseases. Having established phage display in our laboratory, we went on to search for PHD mutants that could bind selected target proteins. This work is described in Chapter 5. We created three PHD libraries with eight randomized residues in each of L1, L3 or in both loops of the PHD. These PHD libraries were then screened against four target proteins. After four rounds of selection, we were able to isolate a PHD mutant (dubbed L13-FH6) that could bind our test protein Fli-ets. This result demonstrates that a novel function can be imparted to the PHD using combinatorial methods and opens the way for further work in applying the PHD scaffold to other protein design work. In summary, the work detailed in Chapters 3 and 5 demonstrates that the PHD possesses many of the properties that are desirable for a protein scaffold for molecular recognition, including small size, stability, and a well-characterised structure. Moreover, the PHD motif possesses two loops (L1 and L3) of substantial size that can be remodeled for target binding. This may lead to an enhancement of binding affinities and specificities over other small scaffolds that have only one variable loop. In light of the fact that PHDs are mainly found in nuclear proteins, it is reasonable to expect that engineered PHDs could be expressed and function in an intracellular environment, unlike many other scaffolds that can only function in an oxidizing environment. Therefore, our results together with other currently available genomic and functional information indicate PHD is an excellent candidate for a scaffold that could be used to modify cellular processes. Appendices 1 and 2 describe completed bodies of work on unrelated projects that I have carried out during the course of my PhD candidature. The first comprises the invention and application of DNA sequences that contain all N-base sequences in the minimum possible length. This work is presented as a reprint of our recently published paper in Nucleic Acids Research. The second Appendix describes our structural analysis of an antifreeze protein from the shorthorn sculpin, a fish that lives in the Arctic and Antarctic oceans. This work is presented as a manuscript that is currently under review at the Journal of the American Chemical Society.
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Chaturvedi, Vineet. "Mechanical Testing and Modeling of the Human Index Finger Distal Pad." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1429272206.
Full textBooks on the topic "PHD finger"
1
Frost, Joy. Under The Lily Pad Bedtime Story: With Finger Puppet (Joy Stories). Joy Stories, 2004.
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2
Great, Be. 1920: Blank Lined Journal; Zeta Phi Beta Sorority; Zeta Phi Beta Merchandise; Z Phi; Finer Woman. Independently Published, 2020.
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Works, Creativity. Finger Paint Paper Pad: 8. 5 X 11 in. 120 Pages, Premium Quality White Paper for Finger-Paint Activity, Cute Finger Painting Pad with Colored Cover for Drawing, Sketching, Painting, Writing or Doodling, Ideal for Kids and Teens . Independently Published, 2022.
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4
Journals, Sisterhood. Born Finer: Zeta Phi Beta Sorority Blank Lined Journal Notebook. Independently Published, 2020.
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MUS, A. N. A. Creative Fingers : Drawing Pad for Kids: Children's SketchBook for Drawing Practice. Independently Published, 2022.
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Journals, Sisterhood. Finer Womanhood: Zeta Phi Beta Blank Ruled Journal Notebook for Soror and Future Soror. Independently Published, 2020.
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Creations, Creative. Zeta Adult Coloring Book: Zeta Phi Beta Sorority Paraphernalia, Finer Woman, Color and Relax. Independently Published, 2021.
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Journals, Sisterhood. Finer 1920: Zeta Phi Beta Blank Ruled Journal Notebook - Best Gift for Soror - Sisterhood. Independently Published, 2020.
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Journals, Sisterhood. Finer Women Graduate 1920: Zeta Phi Beta Sorority Blank Lined Journal Notebook - Best Gift for Graduated Soror. Independently Published, 2020.
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G. Lifestyle G Lifestyle Journals. Finer Women: Zeta Phi Beta Journal for Sorority Sister, Future Soror, Friend, or Family; ZPHI Sorority Paraphernalia for Women; Sorority Gifts. Independently Published, 2019.
Find full textBook chapters on the topic "PHD finger"
1
Gatchalian, Jovylyn, and Tatiana G. Kutateladze. "PHD Fingers as Histone Readers." In Histone Recognition. Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-18102-8_2.
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Sato, Katsunari. "Augmentation of Thermal Sensation on Finger Pad Using Stimuli for Finger Side." In Haptics: Perception, Devices, Control, and Applications. Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-42321-0_48.
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Dzidek, Brygida Maria, Michael Adams, Zhibing Zhang, Simon Johnson, Séréna Bochereau, and Vincent Hayward. "Role of Occlusion in Non-Coulombic Slip of the Finger Pad." In Haptics: Neuroscience, Devices, Modeling, and Applications. Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-44193-0_15.
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Matsuura, Yoichiro, Shogo Okamoto, and Yoji Yamada. "Estimation of Finger Pad Deformation Based on Skin Deformation Transferred to the Radial Side." In Haptics: Neuroscience, Devices, Modeling, and Applications. Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-44196-1_38.
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Moriyama, Taha, and Hiroyuki Kajimoto. "Wearable Haptic Device that Presents the Haptics Sensation of the Finger Pad to the Forearm and Fingertip." In Lecture Notes in Electrical Engineering. Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3194-7_35.
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Tieroyaare Dongdem, Julius, and Cletus Adiyaga Wezena. "Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics." In Hydrolases [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.100534.
Full textAbstract:
E3 ubiquitin ligases of which there are >600 putative in humans, constitute a family of highly heterogeneous proteins and protein complexes that are the ultimate enzymes responsible for the recruitment of an ubiquitin loaded E2 ubiquitin-conjugating enzyme, recognise the appropriate protein substrate and directly or indirectly transfer the ubiquitin load onto the substrate. The aftermath of an E3 ligase activity is usually the formation of an isopeptide bond between the free carboxylate group of ubiquitin’s C-terminal Gly76 and an ε-amino group of the substrate’s Lys, even though non-canonical ubiquitylation on non-amine groups of target proteins have been observed. E3 ligases are grouped into four distinct families: HECT, RING-finger/U-box, RBR and PHD-finger. E3 ubiquitin ligases play critical roles in subcellular signalling cascades in eukaryotes. Dysfunctional E3 ubiquitin ligases therefore tend to inflict dramatic effects on human health and may result in the development of various diseases including Parkinson’s, Amyotrophic Lateral Sclerosis, Alzheimer’s, cancer, etc. Being regulators of numerous cellular processes, some E3 ubiquitin ligases have become potential targets for therapy. This chapter will present a comprehensive review of up-to-date findings in E3 ligases, their role in the pathology of disease and therapeutic potential for future drug development.
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Morrison, E. A., and C. A. Musselman. "The Role of PHD Fingers in Chromatin Signaling." In Chromatin Signaling and Diseases. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-12-802389-1.00007-1.
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Arslan, Yunus Ziya, Yuksel Hacioglu, Yener Taskin, and Nurkan Yagiz. "Control of a Biomimetic Robot Hand Finger." In Advances in Computational Intelligence and Robotics. IGI Global, 2015. http://dx.doi.org/10.4018/978-1-4666-7387-8.ch016.
Full textAbstract:
Due to the dexterous manipulation capability and low metabolic energy consumption property of the human hand, many robotic hands were designed and manufactured that are inspired from the human hand. One of the technical challenges in designing biomimetic robot hands is the control scheme. The control algorithm used in a robot hand is expected to ensure the tracking of reference trajectories of fingertips and joint angles with high accuracy, reliability, and smoothness. In this chapter, trajectory-tracking performances of different types of widely used control strategies (i.e. classical, robust, and intelligent controllers) are comparatively evaluated. To accomplish this evaluation, PID, sliding mode, and fuzzy logic controllers are implemented on a biomimetic robot hand finger model and simulation results are quantitatively analyzed. Pros and cons of the corresponding control algorithms are also discussed.
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Kawasaki, Haruhisa, Shinya Koide, Tetuya Mouri, and Takahiro Endo. "Development of a Finger Pad Force Display for a Hand Haptic Interface." In Virtual Reality. InTech, 2010. http://dx.doi.org/10.5772/13160.
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"Introduction." In Transatlantic Reflections on the Practice-Based PhD in Fine Art. Routledge, 2015. http://dx.doi.org/10.4324/9781315754741-1.
Full textConference papers on the topic "PHD finger"
1
Arima, M., J. Ikari, and T. Tokuhisa. "A Role of the PHD Finger Protein 11 (Phf11) In Functions of Murine T Helper Cells." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4299.
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Zheng, Y.-Z., M.-Z. Xue, H.-J. Shen, et al. "Abstract P2-01-13: The splicing factor PHD finger protein 5A inhibits apoptosis to promote breast cancer progression." In Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-p2-01-13.
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Mascaro, Stephen, Kuo-Wei Chang, and H. Harry Asada. "Finger Touch Sensors Using Instrumented Nails and Their Application to Human-Robot Interactive Control." In ASME 1998 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/imece1998-0238.
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Abstract A new type of touch sensor for detecting contact pressure at human fingertips is presented. Fingernails are instrumented with micro LEDs and photodetectors in order to measure changes in the nail color when the fingers are pressed against a surface. Unlike traditional electronic gloves, in which sensor pads are placed between the fingers and the environment surface, this new sensor allows the fingers to directly contact the environment without being impeded by any object between the finger and the environment. The finger force is detected by measuring changes in the nail color; hence the sensor is mounted on the nail side rather than the finger pad. The technique termed “photoplethysmography” is used for measuring the nail color. A prototype sensor is built and tested, and is used to create a new “free-fingered” electronic glove. The new sensor system is applied to the interface of a cooperative human-robot control system. The information acquired from the finger touch sensors is interpreted within the context of a given task description, and the robot motion is coordinated with the human motion based on the interpreted human behavior. This method is applied to a collaborative task in which a robot equipped with a powered screwdriver assists the human by observing the human hand assembling cable connectors.
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Tada, Mitsunori, and Dinesh K. Pai. "Finger Shell: Predicting Finger Pad Deformation under Line Loading." In 2008 Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems. IEEE, 2008. http://dx.doi.org/10.1109/haptics.2008.4479924.
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Pataky, Todd C., and Vladimir Zatsiorsky. "Finger Pad Viscoelastic Response to Shear Load." In ASME 2003 International Mechanical Engineering Congress and Exposition. ASMEDC, 2003. http://dx.doi.org/10.1115/imece2003-43359.
Full textAbstract:
Uniaxial human skin viscoelasticity has been demonstrated in vitro (Pan et al., 1998). Although some have experimentally measured in vivo finger pad viscoleasticity under normal compression (e.g. Jindirch et al., 2003), none have measured its response to shear load. Knowledge of the viscoelastic properties of the finger pad is important for understanding dynamic finger force coordination during manipulation. While finite element models (FEM) of the finger pad have been developed for dynamic loading studies (e.g. Wu et al., 2002; 2003), these models have not been validated using experimental data. The purpose of the current study was to measure the viscoelastic response of the finger pad to tangential shear load, and to compare the data with results of FEM simulations. The index, middle, ring, and little fingers of the right hand of eight subjects (age: 26.0 ± 2.3 years, height: 175.1 ± 9.5 cm, body mass: 69.3 ± 8.3 kg) were individually clamped at their distal interphalangeal joints in a custom-built device that allowed for compression of the finger pad against a multi-axis force transducer (ATI, North Carolina, USA). The transducer was topped with 100-grit sandpaper to prevent slip; the coefficient of static friction between the finger and the sandpaper was measured to be approximately 1.4. Three different levels of compressive normal force (ranging from 1 to 5 N) were applied to each finger of each subject. Subsequent tangential displacements in both the medial and lateral directions were applied in steps of 0.6 mm (to an accuracy of 0.01 mm) to the force transducer by a micrometer positioning slide (Techno, Inc., NY, USA). Since the micrometer slide was adjusted manually, the loading rate was not precisely controlled (the loading rate was estimated to be 0.6 mm/s). Thus only force relaxation was analyzed (using nonlinear regression techniques) — this was considered sufficient to compare to FEM results. The force response after full relaxation was also considered as a long-term ‘stiffness’ response. The experimental results were compared with two FEM from the literature: Wu et al. (2002) and Wu et al. (2003) that were reconstructed using ABAQUS 6.2 (ABAQUS Inc.; Pawtucket, RI, USA). Both models were 2-D plain strain models with hard normal and rough tangential contact. Both incorporated linearly elastic bone and nail components and had geometry of the average male index finger. The soft tissue of the former FEM was modeled en masse as hyperelastic skin. The soft tissue of latter model incorporated a thin skin layer with biphasic subcutaneous tissue (see the original articles for material parameters, constitutive equations, etc.). The experimental data showed tangential force relaxation on the order of 40% over an average time period of 11.2 seconds. A logarithmic function applied to the rate of change of the force relaxation successfully reproduced the relaxation curves. The long-term ‘stiffness’ was found to be linearly related to the applied shearing displacement magnitude. ANOVA found that both stiffness and the relaxation parameters were different for each finger (p<0.01). These data were also dependent on the direction of the shear load (p<0.01). While the ABAQUS models have been constructed and qualitative agreement has been found between the modeled and experimental results, a quantitative comparison has not yet been performed. The substantial relaxation and inter-finger differences may have important implications to studies of force coordination among redundant fingers. The agreement between experimental data and predictions of FEM confirm the usefulness of the FEM for soft tissue biomechanics studies.
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Galimutti, Peter P., Jerzy T. Sawicki, and David P. Fleming. "Analysis of Finger Seal Lift Pads." In ASME Turbo Expo 2009: Power for Land, Sea, and Air. ASMEDC, 2009. http://dx.doi.org/10.1115/gt2009-59842.
Full textAbstract:
Analyses were performed on finger seal pads having a pressure drop across the pad at right angles to the direction of runner velocity. The film was tapered; the clearance could decrease in both the pressure flow and velocity directions. A substantial load could be carried solely due to the pressure flow; however, the bearing exhibited negative stiffness without film convergence in the velocity flow direction. This is in marked contrast to a full circular bearing or ring seal, where pressure flow alone produces a significant stiffness as long as the clearance converges in the flow direction. The performance of three different pad configurations has been evaluated: aspect ratios L/B of 0.5, 1 (square pad), and 2. Design examples pertaining to each aspect ratio were studied for a gas turbine seal. Results show that lowest leakage, highest load carrying capacity, and highest stiffness are attained for the wide-pad configuration, L/B = 0.5. This paper presents a detailed study of the pad; additional analysis needs to be done for the inclusion of the finger and many other considerations for designing a complete seal.
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Zhang, Hai, Qun Zheng, Guoqiang Yue, and Qingfeng Deng. "Unsteady Numerical Analysis of a Whole Ring of Finger Seal With Grooves on Finger Pads." In ASME Turbo Expo 2013: Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/gt2013-94514.
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This paper presents a numerical investigation of lifting and sealing performance of a whole ring of finger seal with grooving pad structures. Different grooves on the bottom of lifting pad, such as one and two straight grooves, or two herringbone grooves with different gradients etc. are simulated. The rotor vibration is taken into account during the numerical computation. Computational results indicate that the complete ring model is more suitable than an individual finger model to simulate the fluid-solid interactions of the finger seal. Vibration of the rotor changes the deformation pattern of finger seal, and the seal deformation should adapt the clearance in a uniform way according to the rotor position. The grooving pad structures have effects on the leakage flows and the lifting force on the finger. Analytical data revealed the self-adaptive performance of finger seal to rotor vibration. This will be helpful to make the finger seal be of lower wear and smaller leakage in rotational sealing system.
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Zhang, Hai, Qun Zheng, and Guoqiang Yue. "Study on the Leakage and Deformation Characteristics of the Finger Seals by Using Numerical Simulation." In ASME Turbo Expo 2010: Power for Land, Sea, and Air. ASMEDC, 2010. http://dx.doi.org/10.1115/gt2010-23194.
Full textAbstract:
Depending on the throttling process of finger pad gap and the kinetic energy dissipation within the finger gap, finger seal can reduce the fluid leakage. But the deformation of the finger will increase the finger pad gap, which results in the increasing of overall leakage. To evaluate the performances of the finger seal, we used a two-way fluid-structure interaction method to analyse the seal deformation and flow field through the finger seal simultaneously. The numerical analyses show that a strengthened finger seal or a convergent type pad can be considered to reduce the leakage flow through finger pad gap. Finger pad deformation depends mainly on the pressure difference, but not the finger pad gap. There is a strong vortex in the finger gap, which blocks the fluid leakage. The leakage fluid is divided into many small vortices, the kinetic energy of the leakage fluid is dissipated in such a process and its pressure is decreased. When the finger pad deformed, its high pressure end moves toward the shaft, if the pressure difference increases or the shaft oscillated, this end could touch the shaft surface. The position of the maximum radial movement of finger pad does not coincide with the position of the maximum deformation of finger pad, which means the finger pad will be twisted to some extent rather than simply lift.
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Kawasaki, H., S. Koide, T. Mouri, and T. Endo. "Finger pad force display for hand haptic interface." In 2010 IEEE International Conference on Automation Science and Engineering (CASE 2010). IEEE, 2010. http://dx.doi.org/10.1109/coase.2010.5584147.
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Johny, Neethu, and R. Jayagowri. "Performance and Variability Analysis on 7nm FINFET Circuits at Near Threshold." In 2020 2nd PhD Colloquium on Ethically Driven Innovation and Technology for Society (PhD EDITS). IEEE, 2020. http://dx.doi.org/10.1109/phdedits51180.2020.9315308.
Full textReports on the topic "PHD finger"
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Uribe, Fernando R., Alice C. Kilgo, John Mark Grazier, et al. An analysis of the pull strength behaviors of fine-pitch, flip chip solder interconnections using a Au-Pt-Pd thick film conductor on Low-Temperature, Co-fired Ceramic (LTCC) substrates. Office of Scientific and Technical Information (OSTI), 2008. http://dx.doi.org/10.2172/942186.
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Zhang, Hongbin, Shahal Abbo, Weidong Chen, Amir Sherman, Dani Shtienberg, and Frederick Muehlbauer. Integrative Physical and Genetic Mapping of the Chickpea Genome for Fine Mapping and Analysis of Agronomic Traits. United States Department of Agriculture, 2010. http://dx.doi.org/10.32747/2010.7592122.bard.
Full textAbstract:
Chickpea is the third most important pulse crop in the world and ranks first in the Middle East; however, it has been subjected to only limited research in modern genomics. In the first period of this project (US-3034-98R) we constructed two large-insert BAC and BIBAC libraries, developed 325 SSR markers and mapped QTLs controlling ascochyta blight resistance (ABR) and days to first flower (DTF). Nevertheless, the utilities of these tools and results in gene discovery and marker-assisted breeding are limited due to the absence of an essential platform. The goals of this period of the project were to use the resources and tools developed in the first period of the project to develop a BAC/BIBAC physical map for chickpea and using it to identify BAC/BIBACcontigs containing agronomic genes of interest, with an emphasis on ABR and DTF, and develop DNA markers suitable for marker-assisted breeding. Toward these goals, we proposed: 1) Fingerprint ~50,000 (10x) BACs from the BAC and BIBAC libraries, assemble the clones into a genome-wide BAC/BIBAC physical map, and integrate the BAC/BIBAC map with the existing chickpea genetic maps (Zhang, USA); 2) fine-map ABR and DTFQTLs and enhance molecular tools for chickpea genetics and breeding (Shahal, Sherman and DaniShtienberg, Israel; Chen and Muehlbauer; USA); and 3) integrate the BAC/BIBAC map with the existing chickpea genetic maps (Sherman, Israel; Zhang and Chen, USA). For these objectives, a total of $460,000 was requested originally, but a total of $300,000 was awarded to the project. We first developed two new BAC and BIBAC libraries, Chickpea-CME and Chickpea- CHV. The chickpea-CMEBAC library contains 22,272 clones, with an average insert size of 130 kb and equivalent to 4.0 fold of the chickpea genome. The chickpea-CHVBIBAC library contains 38,400 clones, with an average insert size of 140 kb and equivalent to 7.5 fold of the chickpea genome. The two new libraries (11.5 x), along with the two BAC (Chickpea-CHI) and BIBAC (Chickpea-CBV) libraries (7.1 x) constructed in the first period of the project, provide libraries essential for chickpea genome physical mapping and many other genomics researches. Using these four libraries we then developed the proposed BAC/BIBAC physical map of chickpea. A total of 67,584 clones were fingerprinted, and 64,211 (~11.6 x) of the fingerprints validated and used in the physical map assembly. The physical map consists of 1,945 BAC/BIBACcontigs, with each containing an average of 39.2 clones and having an average physical length of 559 kb. The contigs collectively span ~1,088 Mb, being 1.49 fold of the 740- Mb chickpea genome. Third, we integrated the physical map with the two existing chickpea genetic maps using a total of 172 (124 + 48) SSR markers. Fourth, we identified tightly linked markers for ABR-QTL1, increased marker density at ABR-QTL2 and studied the genetic basis of resistance to pod abortion, a major problem in the east Mediterranean, caused by heat stress. Finally, we, using the integrated map, isolated the BAC/BIBACcontigs containing or closely linked to QTL4.1, QTL4.2 and QTL8 for ABR and QTL8 for DTF. The integrated BAC/BIBAC map resulted from the project will provide a powerful platform and tools essential for many aspects of advanced genomics and genetics research of this crop and related species. These includes, but are not limited to, targeted development of SNP, InDel and SSR markers, high-resolution mapping of the chickpea genome and its agronomic genes and QTLs, sequencing and decoding of all genes of the genome using the next-generation sequencing technology, and comparative genome analysis of chickpea versus other legumes. The DNA markers and BAC/BIBACcontigs containing or closely linked to ABR and DTF provide essential tools to develop SSR and SNP markers well-suited for marker-assisted breeding of the traits and clone their corresponding genes. The development of the tools and knowledge will thus promote enhanced and substantial genetic improvement of the crop and related legumes.