To see the other types of publications on this topic, follow the link: Proteine non histone.
Journal articles on the topic 'Proteine non histone'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Proteine non histone.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Traub, Peter, Georg Perides, Siegfried Kühn, and Annemarie Scherbarth. "Interaction in vitro of Non-Epithelial Intermediate Filament Proteins with Histones." Zeitschrift für Naturforschung C 42, no. 1-2 (February 1, 1987): 47–63. http://dx.doi.org/10.1515/znc-1987-1-209.
Full textAbstract:
Abstract Non-epithelial intermediate filament (IF) subunit proteins show a high and specific affinity for core histones at physiological ionic strength. When IF proteins are titrated with a mixture of core histones and linker histone H1, in general the latter is totally excluded from com plexation and in the adducts formed the moderately-arginine-rich histones H2A and H2B are progressively replaced by the very-arginine-rich histones H3 and H4. At histone saturation, 2 molecules of nonneuronal IF protein bind 1 histone HI molecule or 8 core histone m olecules, whereas due to its glutamic acid rich, C terminal extensions one dimer of thp 68 kD npnrofilament nrotein associates with 3 molecules of histone H1 or 24 molecules of core histones. The salt stability of the insoluble association products is dependent on the amount and arginine content of the constituent histone species. Rem oval of the non-α-helical N- and C-terminal polypeptides from IF proteins by partial chymotryptic digestion does not affect their histone-binding characteristics. Since core histones are only partially inactivated by limited tryptic digestion, they also appear to react through their a-helix-rich central domains; the limit peptide derived from histone H1 is com pletely inactive at physiological ionic strength. Affinity chromatography of rod domains of IF proteins on core histone-Sepharose 4B and of histones and their limit peptides on vim entin-Sepharose 4B has shown that the interactions involving fractions of histones H3 and H4 are extrem ely resistant to salt and can be dissociated only with arginine or salt under denaturing conditions. In general, the experim ental results revealed close parallels between the association of histones with IF proteins and their interaction with DNA.
2
Al-Hamashi, Ayad A., Krystal Diaz, and Rong Huang. "Non-Histone Arginine Methylation by Protein Arginine Methyltransferases." Current Protein & Peptide Science 21, no. 7 (September 23, 2020): 699–712. http://dx.doi.org/10.2174/1389203721666200507091952.
Full textAbstract:
Protein arginine methyltransferase (PRMT) enzymes play a crucial role in RNA splicing, DNA damage repair, cell signaling, and differentiation. Arginine methylation is a prominent posttransitional modification of histones and various non-histone proteins that can either activate or repress gene expression. The aberrant expression of PRMTs has been linked to multiple abnormalities, notably cancer. Herein, we review a number of non-histone protein substrates for all nine members of human PRMTs and how PRMT-mediated non-histone arginine methylation modulates various diseases. Additionally, we highlight the most recent clinical studies for several PRMT inhibitors.
3
Kumar, Amish, and Gitanjali Yadav. "Shared ancestry of core-histone subunits and non-histone plant proteins containing the Histone Fold Motif (HFM)." Journal of Bioinformatics and Computational Biology 19, no. 02 (April 2021): 2140001. http://dx.doi.org/10.1142/s0219720021400011.
Full textAbstract:
The three helical Histone Fold Motif (HFM) of core histone proteins provides an evolutionarily favored site for the protein–DNA interface. Despite significant variation in sequence, the HFM retains a distinctive structural fold that has diversified into several non-histone protein families. In this work, we explore the ancestry of non-histone HFM containing families in the plant kingdom. A sequence search algorithm was developed using iterative profile Hidden Markov Models to identify remote homologs of core-histone proteins. The resulting hits were functionally annotated, classified into families, and subjected to comprehensive phylogenetic analyses via Maximum likelihood and Bayesian methods. We have identified 4390 HFM containing proteins in the plant kingdom that are not histones, mostly existing as diverse transcription factor families, distributed widely within and across taxonomic groups. Patterns of homology suggest that core histone subunit H2A has evolved into newer families like NF-YC and DRAP1, whereas the H2B subunit of core histones shares a common ancestry with NF-YB and DR1 class of TFs. Core histone subunits H3 and H4 were found to have evolved into DPE and TAF proteins, respectively. Taken together these results provide insights into diversification events during the evolution of the HFM, including sub-functionalization and neo-functionalization of the HFM.
4
Gong, Ping, Yuetong Wang, and Yongkui Jing. "Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70." International Journal of Molecular Sciences 20, no. 7 (March 30, 2019): 1601. http://dx.doi.org/10.3390/ijms20071601.
Full textAbstract:
Histone deacetylases (HDACs) are a group of enzymes that regulate gene transcription by controlling deacetylation of histones and non-histone proteins. Overexpression of HDACs is found in some types of tumors and predicts poor prognosis. Five HDAC inhibitors are approved for the treatment of cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and multiple myeloma. Treatment with HDAC inhibitors regulates gene expression with increased acetylated histones with unconfirmed connection with therapy. Apoptosis is a key mechanism by which HDAC inhibitors selectively kill cancer cells, probably due to acetylation of non-histone proteins. Ku70 is a protein that repairs DNA breaks and stabilizes anti-apoptotic protein c-FLIP and proapoptotic protein Bax, which is regulated by acetylation. HDAC inhibitors induce Ku70 acetylation with repressed c-FLIP and activated Bax in cancer cells. Current studies indicate that Ku70 is a potential target of HDAC inhibitors and plays an important role during the induction of apoptosis.
5
Xu, Qiutao, Qian Liu, Zhengting Chen, Yaping Yue, Yuan Liu, Yu Zhao, and Dao-Xiu Zhou. "Histone deacetylases control lysine acetylation of ribosomal proteins in rice." Nucleic Acids Research 49, no. 8 (April 9, 2021): 4613–28. http://dx.doi.org/10.1093/nar/gkab244.
Full textAbstract:
Abstract Lysine acetylation (Kac) is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. In this work, we studied mutation effects of rice genes encoding cytoplasm-localized histone deacetylases (HDAC) on protein acetylome and found that the HDAC protein HDA714 was a major deacetylase of the rice non-histone proteins including many ribosomal proteins (r-proteins) and translation factors that were extensively acetylated. HDA714 loss-of-function mutations increased Kac levels but reduced abundance of r-proteins. In vitro and in vivo experiments showed that HDA714 interacted with r-proteins and reduced their Kac. Substitutions of lysine by arginine (depleting Kac) in several r-proteins enhance, while mutations of lysine to glutamine (mimicking Kac) decrease their stability in transient expression system. Ribo-seq analysis revealed that the hda714 mutations resulted in increased ribosome stalling frequency. Collectively, the results uncover Kac as a functional posttranslational modification of r-proteins which is controlled by histone deacetylases, extending the role of Kac in gene expression to protein translational regulation.
6
Bertos, Nicholas R., Audrey H. Wang, and Xiang-Jiao Yang. "Class II histone deacetylases: Structure, function, and regulation." Biochemistry and Cell Biology 79, no. 3 (June 1, 2001): 243–52. http://dx.doi.org/10.1139/o01-032.
Full textAbstract:
Acetylation of histones, as well as non-histone proteins, plays important roles in regulating various cellular processes. Dynamic control of protein acetylation levels in vivo occurs through the opposing actions of histone acetyltransferases and histone deacetylases (HDACs). In the past few years, distinct classes of HDACs have been identified in mammalian cells. Class I members, such as HDAC1, HDAC2, HDAC3, and HDAC8, are well-known enzymatic transcriptional corepressors homologous to yeast Rpd3. Class II members, including HDAC4, HDAC5, HDAC6, HDAC7, and HDAC9, possess domains similar to the deacetylase domain of yeast Hda1. HDAC4, HDAC5, and HDAC7 function as transcriptional corepressors that interact with the MEF2 transcription factors and the N-CoR, BCoR, and CtBP corepressors. Intriguingly, HDAC4, HDAC5, and probably HDAC7 are regulated through subcellular compartmentalization controlled by site-specific phosphorylation and binding of 14-3-3 proteins; the regulation of these HDACs is thus directly linked to cellular signaling networks. Both HDAC6 and HDAC9 possess unique structural modules, so they may have special biological functions. Comprehension of the structure, function, and regulation of class II deacetylases is important for elucidating how acetylation regulates functions of histones and other proteins in vivo.Key words: histone acetylation, protein acetylation, histone deacetylase, 14-3-3 proteins.
7
Li, Hong-Tao, Ting Gong, Zhen Zhou, Yu-Ting Liu, Xiongwen Cao, Yongning He, Charlie Degui Chen, and Jin-Qiu Zhou. "Yeast Hmt1 catalyses asymmetric dimethylation of histone H3 arginine 2 in vitro." Biochemical Journal 467, no. 3 (April 17, 2015): 507–15. http://dx.doi.org/10.1042/bj20141437.
Full textAbstract:
Protein arginine methyltransferases (PRMTs) are a family of enzymes that can methylate protein arginine residues. PRMTs’ substrates include histones and a variety of non-histone proteins. Previous studies have shown that yeast Hmt1 is a type I PRMT and methylates histone H4 arginine 3 and several mRNA-binding proteins. Hmt1 forms dimers or oligomers, but how dimerization or oligomerization affects its activity remains largely unknown. We now report that Hmt1 can methylate histone H3 arginine 2 (H3R2) in vitro. The dimerization but not hexamerization is essential for Hmt1’s activity. Interestingly, the methyltransferase activity of Hmt1 on histone H3R2 requires reciprocal contributions from two Hmt1 molecules. Our results suggest an intermolecular trans-complementary mechanism by which Hmt1 dimer methylates its substrates.
8
Yu, Yucong, Hong Wen, and Xiaobing Shi. "Histone mimics: more tales to read." Biochemical Journal 478, no. 14 (July 23, 2021): 2789–91. http://dx.doi.org/10.1042/bcj20210357.
Full textAbstract:
Post-translational modifications (PTMs) on histone proteins are known as epigenetic marks that demarcate the status of chromatin. These modifications are ‘read' by specific reader proteins, which in turn recruit additional factors to modulate chromatin accessibility and the activity of the underlying DNA. Accumulating evidence suggests that these modifications are not restricted solely to histones, many non-histone proteins may function in a similar way through mimicking the histones. In this commentary, we briefly discuss a systematic study of the discovery of histone H3 N-terminal mimicry proteins (H3TMs), and their implications in chromatin regulation and drug discoveries.
9
WONDRAK, Georg T., Daniel CERVANTES-LAUREAN, Elaine L. JACOBSON, and Myron K. JACOBSON. "Histone carbonylation in vivo and in vitro." Biochemical Journal 351, no. 3 (October 24, 2000): 769–77. http://dx.doi.org/10.1042/bj3510769.
Full textAbstract:
Non-enzymic damage to nuclear proteins has potentially severe consequences for the maintenance of genomic integrity. Introduction of carbonyl groups into histones in vivo and in vitro was assessed by Western blot immunoassay and reductive incorporation of tritium from radiolabelled NaBH4 (sodium borohydride). Histone H1 extracted from bovine thymus, liver and spleen was found to contain significantly elevated amounts of protein-bound carbonyl groups as compared with core histones. The carbonyl content of nuclear proteins of rat pheochromocytoma cells (PC12 cells) was not greatly increased following oxidative stress induced by H2O2, but was significantly increased following alkylating stress induced by N-methyl-N´-nitro-N-nitrosoguanidine or by combined oxidative and alkylating stress. Free ADP-ribose, a reducing sugar generated in the nucleus in proportion to DNA strand breaks, was shown to be a potent histone H1 carbonylating agent in isolated PC12 cell nuclei. Studies of the mechanism of histone H1 modification by ADP-ribose indicate that carbonylation involves formation of a stable acyclic ketoamine. Our results demonstrate preferential histone H1 carbonylation in vivo, with potentially important consequences for chromatin structure and function.
10
Demyanenko, Svetlana, and Svetlana Sharifulina. "The Role of Post-Translational Acetylation and Deacetylation of Signaling Proteins and Transcription Factors after Cerebral Ischemia: Facts and Hypotheses." International Journal of Molecular Sciences 22, no. 15 (July 26, 2021): 7947. http://dx.doi.org/10.3390/ijms22157947.
Full textAbstract:
Histone deacetylase (HDAC) and histone acetyltransferase (HAT) regulate transcription and the most important functions of cells by acetylating/deacetylating histones and non-histone proteins. These proteins are involved in cell survival and death, replication, DNA repair, the cell cycle, and cell responses to stress and aging. HDAC/HAT balance in cells affects gene expression and cell signaling. There are very few studies on the effects of stroke on non-histone protein acetylation/deacetylation in brain cells. HDAC inhibitors have been shown to be effective in protecting the brain from ischemic damage. However, the role of different HDAC isoforms in the survival and death of brain cells after stroke is still controversial. HAT/HDAC activity depends on the acetylation site and the acetylation/deacetylation of the main proteins (c-Myc, E2F1, p53, ERK1/2, Akt) considered in this review, that are involved in the regulation of cell fate decisions. Our review aims to analyze the possible role of the acetylation/deacetylation of transcription factors and signaling proteins involved in the regulation of survival and death in cerebral ischemia.
11
Zhiteneva, Alisa, Juan Jose Bonfiglio, Alexandr Makarov, Thomas Colby, Paola Vagnarelli, Eric C. Schirmer, Ivan Matic, and William C. Earnshaw. "Mitotic post-translational modifications of histones promote chromatin compaction in vitro." Open Biology 7, no. 9 (September 2017): 170076. http://dx.doi.org/10.1098/rsob.170076.
Full textAbstract:
How eukaryotic chromosomes are compacted during mitosis has been a leading question in cell biology since the nineteenth century. Non-histone proteins such as condensin complexes contribute to chromosome shaping, but appear not to be necessary for mitotic chromatin compaction. Histone modifications are known to affect chromatin structure. As histones undergo major changes in their post-translational modifications during mitotic entry, we speculated that the spectrum of cell-cycle-specific histone modifications might contribute to chromosome compaction during mitosis. To test this hypothesis, we isolated core histones from interphase and mitotic cells and reconstituted chromatin with them. We used mass spectrometry to show that key post-translational modifications remained intact during our isolation procedure. Light, atomic force and transmission electron microscopy analysis showed that chromatin assembled from mitotic histones has a much greater tendency to aggregate than chromatin assembled from interphase histones, even under low magnesium conditions where interphase chromatin remains as separate beads-on-a-string structures. These observations are consistent with the hypothesis that mitotic chromosome formation is a two-stage process with changes in the spectrum of histone post-translational modifications driving mitotic chromatin compaction, while the action of non-histone proteins such as condensin may then shape the condensed chromosomes into their classic mitotic morphology.
12
Habibian, Justine, and Bradley Ferguson. "The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart." International Journal of Molecular Sciences 20, no. 1 (December 28, 2018): 102. http://dx.doi.org/10.3390/ijms20010102.
Full textAbstract:
Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.
13
Warren, Christopher, Jeffrey B. Bonanno, Steven C. Almo, and David Shechter. "Structure of a single-chain H2A/H2B dimer." Acta Crystallographica Section F Structural Biology Communications 76, no. 5 (April 28, 2020): 194–98. http://dx.doi.org/10.1107/s2053230x20004604.
Full textAbstract:
Chromatin is the complex assembly of nucleic acids and proteins that makes up the physiological form of the eukaryotic genome. The nucleosome is the fundamental repeating unit of chromatin, and is composed of ∼147 bp of DNA wrapped around a histone octamer formed by two copies of each core histone: H2A, H2B, H3 and H4. Prior to nucleosome assembly, and during histone eviction, histones are typically assembled into soluble H2A/H2B dimers and H3/H4 dimers and tetramers. A multitude of factors interact with soluble histone dimers and tetramers, including chaperones, importins, histone-modifying enzymes and chromatin-remodeling enzymes. It is still unclear how many of these proteins recognize soluble histones; therefore, there is a need for new structural tools to study non-nucleosomal histones. Here, a single-chain, tailless Xenopus H2A/H2B dimer was created by directly fusing the C-terminus of H2B to the N-terminus of H2A. It is shown that this construct (termed scH2BH2A) is readily expressed in bacteria and can be purified under non-denaturing conditions. A 1.31 Å resolution crystal structure of scH2BH2A shows that it adopts a conformation that is nearly identical to that of nucleosomal H2A/H2B. This new tool is likely to facilitate future structural studies of many H2A/H2B-interacting proteins.
14
Pardal, Alonso J., Filipe Fernandes-Duarte, and Andrew J. Bowman. "The histone chaperoning pathway: from ribosome to nucleosome." Essays in Biochemistry 63, no. 1 (March 22, 2019): 29–43. http://dx.doi.org/10.1042/ebc20180055.
Full textAbstract:
AbstractNucleosomes represent the fundamental repeating unit of eukaryotic DNA, and comprise eight core histones around which DNA is wrapped in nearly two superhelical turns. Histones do not have the intrinsic ability to form nucleosomes; rather, they require an extensive repertoire of interacting proteins collectively known as ‘histone chaperones’. At a fundamental level, it is believed that histone chaperones guide the assembly of nucleosomes through preventing non-productive charge-based aggregates between the basic histones and acidic cellular components. At a broader level, histone chaperones influence almost all aspects of chromatin biology, regulating histone supply and demand, governing histone variant deposition, maintaining functional chromatin domains and being co-factors for histone post-translational modifications, to name a few. In this essay we review recent structural insights into histone-chaperone interactions, explore evidence for the existence of a histone chaperoning ‘pathway’ and reconcile how such histone-chaperone interactions may function thermodynamically to assemble nucleosomes and maintain chromatin homeostasis.
15
Vasileva, Bela, Dessislava Staneva, Natalia Krasteva, George Miloshev, and Milena Georgieva. "Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging." Cells 10, no. 7 (July 11, 2021): 1755. http://dx.doi.org/10.3390/cells10071755.
Full textAbstract:
Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.
16
Bernardes, Natalia Elisa, and Yuh Min Chook. "Nuclear import of histones." Biochemical Society Transactions 48, no. 6 (December 10, 2020): 2753–67. http://dx.doi.org/10.1042/bst20200572.
Full textAbstract:
The transport of histones from the cytoplasm to the nucleus of the cell, through the nuclear membrane, is a cellular process that regulates the supply of new histones in the nucleus and is key for DNA replication and transcription. Nuclear import of histones is mediated by proteins of the karyopherin family of nuclear transport receptors. Karyopherins recognize their cargos through linear motifs known as nuclear localization/export sequences or through folded domains in the cargos. Karyopherins interact with nucleoporins, proteins that form the nuclear pore complex, to promote the translocation of their cargos into the nucleus. When binding to histones, karyopherins not only function as nuclear import receptors but also as chaperones, protecting histones from non-specific interactions in the cytoplasm, in the nuclear pore and possibly in the nucleus. Studies have also suggested that karyopherins might participate in histones deposition into nucleosomes. In this review we describe structural and biochemical studies from the last two decades on how karyopherins recognize and transport the core histone proteins H3, H4, H2A and H2B and the linker histone H1 from the cytoplasm to the nucleus, which karyopherin is the major nuclear import receptor for each of these histones, the oligomeric state of histones during nuclear import and the roles of post-translational modifications, histone-chaperones and RanGTP in regulating these nuclear import pathways.
17
Ryan, J., A. J. Llinas, D. A. White, B. M. Turner, and J. Sommerville. "Maternal histone deacetylase is accumulated in the nuclei of Xenopus oocytes as protein complexes with potential enzyme activity." Journal of Cell Science 112, no. 14 (July 15, 1999): 2441–52. http://dx.doi.org/10.1242/jcs.112.14.2441.
Full textAbstract:
Reversible acetylation of core histones plays an important regulatory role in transcription and replication of chromatin. The acetylation status of chromatin is determined by the equilibrium between activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The Xenopus protein HDACm shows sequence homology to other putative histone deacetylases, but its mRNA is expressed only during early development. Both HDACm protein and acetylated non-chromosomal histones are accumulated in developing oocytes, indicating that the key components for histone deposition into new chromatin during blastula formation are in place by the end of oogenesis. Here we show that the 57 kDa HDACm protein undergoes steady accumulation in the nucleus, where it is organized in a multiprotein complex of approx. 300 kDa. A second, major component of the nuclear complex is the retinoblastoma-associated protein p48 (RbAp48/46), which may be used as an adaptor to contact acetylated histones in newly assembled chromatin. The nuclear complex has HDAC activity that is sensitive to trichostatin A, zinc ions and phosphatase treatment. The 57 kDa protein serves as a marker for total HDAC activity throughout oogenesis and early embryogenesis. The active HDACm complex and its acetylated histone substrates appear to be kept apart until after chromatin assembly has taken place. However, recombinant HDACm, injected into the cytoplasm of oocytes, not only is translocated to the nucleus, but also is free to interact with the endogenous chromatin.
18
Khan, Ahlia N., and Peter N. Lewis. "Unstructured Conformations Are a Substrate Requirement for the Sir2 Family of NAD-dependent Protein Deacetylases." Journal of Biological Chemistry 280, no. 43 (August 29, 2005): 36073–78. http://dx.doi.org/10.1074/jbc.m508247200.
Full textAbstract:
The regulation of protein function is often achieved through post-translational modifications including phosphorylation, methylation, ubiquitination, and acetylation. The role of acetylation has been most extensively studied in the context of histones, but it is becoming increasingly evident that this modification now includes other proteins. The Sir2 family of NAD-dependent deacetylases was initially recognized as mediating gene silencing through histone deacetylation, but several family members display non-nuclear sub-cellular localization and deacetylate non-histone protein substrates. Although many structural and enzymatic studies of Sir2 proteins have been reported, how substrate recognition is achieved by this family of enzymes is unknown. Here we use in vitro deacetylase assays and a variety of potential substrates to examine the substrate specificity of yeast homologue Hst2. We show that Hst2 is specific for acetyl-lysine within proteins; it does not deacetylate small polycations such as acetyl-spermine or acetylated amino ter-mini of proteins. Furthermore we have found that Hst2 displays conformational rather than sequence specificity, preferentially deacetylating acetyl-lysine within unstructured regions of proteins. Our results suggest that this conformational requirement may be a general feature for substrate recognition in the Sir2 family.
19
Mendiratta, Shweta, Alberto Gatto, and Genevieve Almouzni. "Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle." Journal of Cell Biology 218, no. 1 (September 26, 2018): 39–54. http://dx.doi.org/10.1083/jcb.201807179.
Full textAbstract:
As the building blocks of chromatin, histones are central to establish and maintain particular chromatin states associated with given cell fates. Importantly, histones exist as distinct variants whose expression and incorporation into chromatin are tightly regulated during the cell cycle. During S phase, specialized replicative histone variants ensure the bulk of the chromatinization of the duplicating genome. Other non-replicative histone variants deposited throughout the cell cycle at specific loci use pathways uncoupled from DNA synthesis. Here, we review the particular dynamics of expression, cellular transit, assembly, and disassembly of replicative and non-replicative forms of the histone H3. Beyond the role of histone variants in chromatin dynamics, we review our current knowledge concerning their distinct regulation to control their expression at different levels including transcription, posttranscriptional processing, and protein stability. In light of this unique regulation, we highlight situations where perturbations in histone balance may lead to cellular dysfunction and pathologies.
20
Sakurai, A., K. Ichikawa, K. Hashizume, T. Miyamoto, K. Yamauchi, H. Ohtsuka, Y. Nishii, and T. Yamada. "Possible role of histones in the organization of rat liver thyroid hormone receptors in chromatin." Journal of Endocrinology 121, no. 2 (May 1989): 337–41. http://dx.doi.org/10.1677/joe.0.1210337.
Full textAbstract:
ABSTRACT The effects of histone subfractions on rat liver thyroid hormone receptor–DNA interaction were examined using an in-vitro DNA-cellulose binding assay. H1 histones bound to DNA showed reversible and potent inhibition of receptor–DNA binding without affecting receptor–hormone binding. Poly-lysine, bovine serum albumin, ovalbumin and cytochrome c did not alter receptor–DNA binding. H1 histone subfractions (calf thymus lysine-rich histone (CTL)-1, CTL-2 and CTL-3) showed potent inhibition of receptor–DNA binding indistinguishable from each other. The quantity of H1 histone subfractions bound to DNA was the same. Although each subfraction has different functional properties, inhibition of receptor–DNA binding was a common feature of all the H1 histone subfractions, which is important for the non-random distribution of the receptor in chromatin. Binding of the receptor to core histones was investigated; it was found to bind to core histones more potently than to other proteins (H1 histone, ovalbumin and cytochrome c). Among core histone subfractions, H4 histone bound to the receptor most potently and is the candidate to be one of the acceptor sites of the receptor in chromatin. Journal of Endocrinology (1989) 121, 337–341
21
Meheus, L. A., J. J. Van Beeumen, A. V. Coomans, and J. R. Vanfleteren. "Age-specific nuclear proteins in the nematode worm Caenorhabditis elegans." Biochemical Journal 245, no. 1 (July 1, 1987): 257–61. http://dx.doi.org/10.1042/bj2450257.
Full textAbstract:
The nematode worm Caenorhabditis elegans is known to undergo characteristic morphological as well as physiological signs of senescence. Two-dimensional gel electrophoresis shows that alterations also occur in the pattern of the nuclear proteins as a function of age. Non-histone proteins whose level exhibits a steep fall with age are egg-specific and not involved in senescence. However, a distinct set of non-histones accumulates with age and can be considered as senescence markers. Some of these are glycoproteins, as shown by their concanavalin A-binding properties. One age-specific polypeptide, called ‘protein S-28’, was further characterized by peptide mapping and determination of its N-terminal amino acid sequence.
22
Geraldo, Nuno, and Rita Abranches. "Immunolocalization of Histone Modifications as a Tool to Visualize Chromatin Dynamics in Plants." Microscopy and Microanalysis 14, S3 (September 2008): 130–33. http://dx.doi.org/10.1017/s1431927608089642.
Full textAbstract:
The nuclear DNA of eukaryotic organisms is associated with several proteins. These proteins together with the DNA form chromatin. In all eukaryotes, DNA is folded around a core of histones to form nucleosomes. Chromatin was previously believed to serve mainly to organize and compact the genetic material. However, in recent years, chromatin has been regarded has a highly dynamic structure responsible for controlling gene expression. Therefore, chromatin is highly flexible, to make genetic information accessible when needed, and the degree of compaction has to be tightly regulated. DNA staining, using 4',6-diamidino-2-phenylindole (DAPI), provided the basis for a cytological distinction between weakly stained euchromatin, now known to be gene rich, and brightly stained heterochromatin, which usually contains various repetitive sequences. In many organisms, heterochromatic DNA is hypermethylated and this is used as an additional mechanism to regulate transcription. Histones can be modified by acetylation, phosphorylation, methylation or ubiquitination. These mechanisms provide signals to which other factors can bind and additionally alter the biochemical properties of chromatin (i.e., “histone code”). In general, acetylation of histones is correlated with active genes, whereas methylation of histones at different positions results in changes in gene expression. The methylation of lysine 9 in histone 3 (H3K9) is associated with heterochromatin formation while methylation of lysine 4 of histone 3 (H3K4) methylation is related to gene activation and positioned in euchromatin. DNA and histone modifications recruit various non-histone proteins to specific chromosomal regions and eventually create a defined nuclear structure that is able to affect gene expression.
23
Jiang, Xuanzhao, Tatiana A. Soboleva, and David J. Tremethick. "Short Histone H2A Variants: Small in Stature but not in Function." Cells 9, no. 4 (April 2, 2020): 867. http://dx.doi.org/10.3390/cells9040867.
Full textAbstract:
The dynamic packaging of DNA into chromatin regulates all aspects of genome function by altering the accessibility of DNA and by providing docking pads to proteins that copy, repair and express the genome. Different epigenetic-based mechanisms have been described that alter the way DNA is organised into chromatin, but one fundamental mechanism alters the biochemical composition of a nucleosome by substituting one or more of the core histones with their variant forms. Of the core histones, the largest number of histone variants belong to the H2A class. The most divergent class is the designated “short H2A variants” (H2A.B, H2A.L, H2A.P and H2A.Q), so termed because they lack a H2A C-terminal tail. These histone variants appeared late in evolution in eutherian mammals and are lineage-specific, being expressed in the testis (and, in the case of H2A.B, also in the brain). To date, most information about the function of these peculiar histone variants has come from studies on the H2A.B and H2A.L family in mice. In this review, we describe their unique protein characteristics, their impact on chromatin structure, and their known functions plus other possible, even non-chromatin, roles in an attempt to understand why these peculiar histone variants evolved in the first place.
24
Davie, J. R., and G. P. Delcuve. "Characterization and chromatin distribution of the H1 histones and high-mobility-group non-histone chromosomal proteins of trout liver and hepatocellular carcinoma." Biochemical Journal 280, no. 2 (December 1, 1991): 491–97. http://dx.doi.org/10.1042/bj2800491.
Full textAbstract:
The H1 histones serve as general repressors of gene expression by inducing the formation of a compact chromatin structure, whereas the high-mobility-group (HMG) non-histone chromosomal proteins have roles in maintaining the structure and function of transcriptionally active chromatin. The distribution of the H1 histone subtypes and HMG proteins among various trout tissues (liver, hepatocellular carcinoma, testis and erythrocyte) was determined. Histone H1b was present in the chromatin of liver, but not in the chromatin of hepatocellular carcinoma, testis or erythrocyte. Nuclease-resistant regions of liver chromatin had elevated levels of histone H1b. Histone H1b was isolated, and the N-terminal amino acid sequence of histone H1b was found to be highly similar to that of mammalian histone H1(0) and duck H5. HMG proteins T1, T2, T3, H6, C, D and F were associated with liver and hepatocellular-carcinoma chromatin, with hepatocellular carcinoma containing higher levels of HMG T1 and F. Testis and erythrocyte had HMG T2 and H6 as their predominant HMG proteins. Most of the HMG H6 of hepatocellular carcinoma, but not of liver, was located in a chromatin fraction that was soluble at physiological ionic strength and enriched in transcriptionally active DNA. These alterations in the chromatin distribution and content of hepatocyte HMG proteins and H1 histone subtypes may contribute to aberrant hepatocyte gene expression in the hepatocellular carcinoma.
25
Pogorelova, T. N., V. O. Gunko, A. A. Nikashina, A. A. Mikhelson, I. A. Alliluev, and A. V. Larichkin. "Impairment of production and posttranslational changes of placental nuclear and membrane proteins with complicated pregnancy." Biomeditsinskaya Khimiya 65, no. 6 (2019): 513–19. http://dx.doi.org/10.18097/pbmc20196506513.
Full textAbstract:
The content of nuclear and membrane proteins of the placenta, as well as posttranslational modification of these proteins in physiological pregnancy and placental insufficiency (PI) were studied. Differential centrifugation, electrophoresis in polyacrylamide gel, spectrophotometric methods were used. It was found that with PN there is a decrease in the degree of production of the studied proteins of varying degrees relative to control parameters. For chromatin proteins, a more pronounced decrease in the content of non-histone proteins was found in comparison with histones. Among histone fractions, the maximum decrease was detected in the H2A fraction. The degree of change in the amount of membrane proteins depends on the detergent used. Changes in posttranslational protein modifications disorders are characterized by a decrease in the content of amine and amide (especially difficult to hydrolyze) groups and an increase in carbonyl derivatives of proteins. The revealed changes in the composition and structure of the nuclear and membrane proteins of the placenta, performing numerous regulatory functions, can be triggering links in the chain of molecular damage in the placenta at PI.
26
Fonin, Alexander V., Olga V. Stepanenko, Irina M. Kuznetsova, Konstantin K. Turoverov, Elena I. Kostyleva, and Vladimir I. Vorobyev. "Interaction between linker histone H1 and non-histone chromatin protein HMGB1." Spectroscopy 24, no. 1-2 (2010): 165–68. http://dx.doi.org/10.1155/2010/745671.
Full textAbstract:
The possibility of interaction between linker histone H1 and non-histone chromatin protein HMGB1 was studied by intrinsic UV-fluorescence, far and near-UV CD and light scattering. The obtained data allow us to assume that the increase of histone H1 content in the HMGB1 solutions in a low ionic strength is accompanied by the destruction of HMGB1 associates. The interaction between proteins causes the increase of ordered regions in the protein molecules and the minor changes in their tertiary structure.
27
Nicholson, Thomas B., and Taiping Chen. "LSD1 demethylates histone and non-histone proteins." Epigenetics 4, no. 3 (April 30, 2009): 129–32. http://dx.doi.org/10.4161/epi.4.3.8443.
Full text
28
Song, Wan, Nóra Zsindely, Anikó Faragó, J. Lawrence Marsh, and László Bodai. "Systematic genetic interaction studies identify histone demethylase Utx as potential target for ameliorating Huntington’s disease." Human Molecular Genetics 27, no. 4 (December 21, 2017): 649–66. http://dx.doi.org/10.1093/hmg/ddx432.
Full textAbstract:
Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by alterations in the huntingtin gene (htt). Transcriptional dysregulation is an early event in HD progression. Protein acetylation and methylation particularly on histones regulates chromatin structure thereby preventing or facilitating transcription. Although protein acetylation has been found to affect HD symptoms, little is known about the potential role of protein methylation in HD pathology. In recent years, a series of proteins have been described that are responsible for methylating and demethylating histones as well as other proteins. We carried out systematic genetic interaction studies testing lysine and arginine methylases and demethylases in a Drosophila melanogaster HD model. We found that modulating methylation enzymes that typically affect histone positions H3K4, H3K36 or H3K79 had varying effects on HD pathology while modulating ones that typically affect constitutive heterochromatin marks at H3K9 and H4K20 generally had limited impact on HD pathology. In contrast, modulating enzymes acting on the facultative heterochromatin mark at H3K27 had specific effects on HD pathology, with reduction of the demethylase Utx rescuing HTT-induced pathology while reducing Polycomb Repressive Complex2 core methylase components led to more aggressive pathology. Further exploration of the mechanism underlying the methylation-specific interactions suggest that these lysine and arginine methylases and demethylases are likely exerting their influence through non-histone targets. These results highlight a novel therapeutic approach for HD in the form of Utx inhibition.
29
Nair, Divya R., and Elizabeth Bhoj. "3548 De novo germline variants in Histone 3 Family 3A (H3F3A) and Histone 3 Family 3B (H3F3B) cause a severe neurodegenerative disorder and functional effects unique from their somatic mutations." Journal of Clinical and Translational Science 3, s1 (March 2019): 103. http://dx.doi.org/10.1017/cts.2019.235.
Full textAbstract:
OBJECTIVES/SPECIFIC AIMS: Histones are nuclear proteins that associate with DNA to facilitate packaging into condensed chromatin. Histones are dynamically decorated with post-translational modifications (PTMs), which regulate such processes as DNA repair, gene expression, mitosis, and meiosis. Histone 3 Family 3 (H3F3) histones (H3.3), encoded by H3F3A and H3F3B, mark active genes, maintain epigenetic memory, and maintain heterochromatin and telomeric integrity. Specific somatic mutations in H3F3A and H3F3B have been strongly associated with pediatric glia and other tumors, but no germline mutations have been reported. The goal of our study was to further understand the functional effects of germline mutations of H3F3A and H3F3B. METHODS/STUDY POPULATION: We analyzed 32 patients bearing de novo germline missense mutations in H3F3A or H3F3B with core phenotypes of progressive neurologic dysfunction and congenital anomalies, but no malignancies. Patient histones were analyzed by quantitative mass spectrometry (qMS). RESULTS/ANTICIPATED RESULTS: qMS results revealed that the mutant histone proteins are present at a concentration similar to that of wild-type H3.3. qMS analysis showed strikingly aberrant PTM patterns that suggested local dysregulation. These patterns are distinct from the dominant negative somatic mutations, which cause more global PTM dysregulation. Patient cells also demonstrated upregulation of the expression of genes related to mitosis and cell division, and had a greater proliferative capacity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests that the pathogenic mechanism of germline histone mutations is distinct from that of the published cancer-associated somatic histone mutations, but may converge on control of cell proliferation. Further clarification of the pathophysiology in these patients can elucidate the roles of histones and histone PTMs in human development and non-syndromic neurodegeneration. In addition, it provides a framework for targeted therapy development for this and related progressive neurologic disorders.
30
Czupryn, Marta, Kenneth H. Falchuk, and Bert L. Vallee. "Zinc deficiency and metabolism of histones and non-histone proteins in Euglena gracilis." Biochemistry 26, no. 25 (December 1987): 8263–69. http://dx.doi.org/10.1021/bi00399a037.
Full text
31
Lee, Tzong-Yi, Cheng-Wei Chang, Cheng-Tzung Lu, Tzu-Hsiu Cheng, and Tzu-Hao Chang. "Identification and characterization of lysine-methylated sites on histones and non-histone proteins." Computational Biology and Chemistry 50 (June 2014): 11–18. http://dx.doi.org/10.1016/j.compbiolchem.2014.01.009.
Full text
32
Wallberg, A. E., E. M. Flinn, J. Å. Gustafsson, and A. P. H. Wright. "Recruitment of chromatin remodelling factors during gene activation via the glucocorticoid receptor N-terminal domain." Biochemical Society Transactions 28, no. 4 (August 1, 2000): 410–14. http://dx.doi.org/10.1042/bst0280410.
Full textAbstract:
We have shown that yeast mutants with defects in the Ada adaptor proteins are defective in hormone-dependent gene activation by ectopically expressed human glucocorticoid receptor (GR). Others have shown that the Ada2 protein is required for physical interactions between some activation domains and TBP (TATA-binding protein), whereas the Gcn5 (Ada4) protein has a histone acetyltransferase (HAT) activity. Although all HAT enzymes are able to acetylate histone substrates, some also acetylate non-histone proteins. Taken together, these observations suggest that the Ada proteins have the ability to effect different steps in the process of gene activation. It has recently been shown that the Ada proteins are present in two distinct protein complexes, the Ada complex and a larger SAGA complex. Our recent work has focused on determining (1) which of the Ada-containing complexes mediates gene activation by GR, (2) whether the HAT activity encoded by GCN5 is required for GR-dependent gene activation, (3) whether the Ada proteins contribute to GR-mediated activation at the level of chromatin remodelling and (4) how the role of these HAT complexes is integrated with other chromatin remodelling activities during GR-mediated gene activation. Our results suggest a model in which GR recruits the SAGA complex and that this contributes to chromatin remodelling via a mechanism involving the acetylation of histones. Furthermore, recruitment of the SWI/SNF remodelling complex also has a role in GR-mediated activation that is independent of the role of SAGA. These complexes are similar to analogous mammalian complexes and therefore these results are likely to be relevant to the human system.
33
Riedel, N., and H. Fasold. "Nuclear-envelope vesicles as a model system to study nucleocytoplasmic transport. Specific uptake of nuclear proteins." Biochemical Journal 241, no. 1 (January 1, 1987): 213–19. http://dx.doi.org/10.1042/bj2410213.
Full textAbstract:
In the preceding paper [Riedel & Fasold (1987) Biochem. J. 241, 203-212] we have described a procedure for the preparation of nuclear-envelope vesicles (NE vesicles) from rat liver nuclei. These vesicles, which are largely free of components of the nuclear interior, were employed in an assay system in vitro to study protein translocation across the NE. We found that nuclear proteins such as histones, high-mobility-group proteins and acidic chromosomal proteins are specifically taken up and accumulated in the NE vesicles, whereas there is little or no affinity for non-nuclear proteins like immunoglobulin, myoglobin and cytochrome c. The kinetics of histone uptake into the NE vesicles are similar to those obtained for whole rat liver nuclei, and comparative studies with non-vesicular NEs prepared by deoxyribonuclease I-treatment (DNAase-NEs) indicate that the NE of the vesicles affects the uptake kinetics and increases the capacity for nuclear proteins. The uptake of histones into NE vesicles, but not the binding to DNAase-NEs, can be stimulated by GTP and GDP. Furthermore, we found that even very large molecules can be entrapped in the vesicles during their preparation. These results indicate that the NE vesicles might provide a useful system in vitro with which to investigate the structures and mechanisms involved in protein translocation across the NE.
34
Chikhirzhina, Elena, Tatyana Starkova, Anton Beljajev, Alexander Polyanichko, and Alexey Tomilin. "Functional Diversity of Non-Histone Chromosomal Protein HmgB1." International Journal of Molecular Sciences 21, no. 21 (October 26, 2020): 7948. http://dx.doi.org/10.3390/ijms21217948.
Full textAbstract:
The functioning of DNA in the cell nucleus is ensured by a multitude of proteins, whose interactions with DNA as well as with other proteins lead to the formation of a complicated, organized, and quite dynamic system known as chromatin. This review is devoted to the description of properties and structure of the progenitors of the most abundant non-histone protein of the HMGB family—the HmgB1 protein. The proteins of the HMGB family are also known as “architectural factors” of chromatin, which play an important role in gene expression, transcription, DNA replication, and repair. However, as soon as HmgB1 goes outside the nucleus, it acquires completely different functions, post-translational modifications, and change of its redox state. Despite a lot of evidence of the functional activity of HmgB1, there are still many issues to be solved related to the mechanisms of the influence of HmgB1 on the development and treatment of different diseases—from oncological and cardiovascular diseases to pathologies during pregnancy and childbirth. Here, we describe molecular structure of the HmgB1 protein and discuss general mechanisms of its interactions with other proteins and DNA in cell.
35
Bach, Svitlana V., and Ashok N. Hegde. "The proteasome and epigenetics: zooming in on histone modifications." Biomolecular Concepts 7, no. 4 (August 1, 2016): 215–27. http://dx.doi.org/10.1515/bmc-2016-0016.
Full textAbstract:
AbstractThe proteasome is a structural complex of many proteins that degrades substrates marked by covalent linkage to ubiquitin. Many years of research has shown a role for ubiquitin-proteasome-mediated proteolysis in synaptic plasticity and memory mainly in degrading synaptic, cytoplasmic and nuclear proteins. Recent work indicates that the proteasome has wider proteolytic and non-proteolytic roles in processes such as histone modifications that affect synaptic plasticity and memory. In this review, we assess the evidence gathered from neuronal as well as non-neuronal cell types regarding the function of the proteasome in positive or negative regulation of posttranslational modifications of histones, such as acetylation, methylation and ubiquitination. We discuss the critical roles of the proteasome in clearing excess histone proteins in various cellular contexts and the possible non-proteolytic functions in regulating transcription of target genes. In addition, we summarize the current literature on diverse chromatin-remodeling machineries, such as histone acetyltransferases, deacetylates, methyltransferases and demethylases, as targets for proteasomal degradation across experimental models. Lastly, we provide a perspective on how proteasomal regulation of histone modifications may modulate synaptic plasticity in the nervous system.
36
Zhao, Linhong, Junaid Ali Shah, Yong Cai, and Jingji Jin. "‘O-GlcNAc Code’ Mediated Biological Functions of Downstream Proteins." Molecules 23, no. 8 (August 6, 2018): 1967. http://dx.doi.org/10.3390/molecules23081967.
Full textAbstract:
As one of the post-translational modifications, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) often occurs on serine (Ser) and threonine (Thr) residues of specific substrate cellular proteins via the addition of O-GlcNAc group by O-GlcNAc transferase (OGT). Maintenance of normal intracellular levels of O-GlcNAcylation is controlled by OGT and glycoside hydrolase O-GlcNAcase (OGA). Unbalanced O-GlcNAcylation levels have been involved in many diseases, including diabetes, cancer, and neurodegenerative disease. Recent research data reveal that O-GlcNAcylation at histones or non-histone proteins may provide recognition platforms for subsequent protein recruitment and further initiate intracellular biological processes. Here, we review the current understanding of the ‘O-GlcNAc code’ mediated intracellular biological functions of downstream proteins.
37
Vlachonasios, Konstantinos, Stylianos Poulios, and Niki Mougiou. "The Histone Acetyltransferase GCN5 and the Associated Coactivators ADA2: From Evolution of the SAGA Complex to the Biological Roles in Plants." Plants 10, no. 2 (February 5, 2021): 308. http://dx.doi.org/10.3390/plants10020308.
Full textAbstract:
Transcription of protein-encoding genes starts with forming a pre-initiation complex comprised of RNA polymerase II and several general transcription factors. To activate gene expression, transcription factors must overcome repressive chromatin structure, which is accomplished with multiprotein complexes. One such complex, SAGA, modifies the nucleosomal histones through acetylation and other histone modifications. A prototypical histone acetyltransferase (HAT) known as general control non-repressed protein 5 (GCN5), was defined biochemically as the first transcription-linked HAT with specificity for histone H3 lysine 14. In this review, we analyze the components of the putative plant SAGA complex during plant evolution, and current knowledge on the biological role of the key components of the HAT module, GCN5 and ADA2b in plants, will be summarized.
38
Dong, Wenbo, Punit Prasad, Andreas Lennartsson, and Karl Ekwall. "The Role of Non-Catalytic Domains of Hrp3 in Nucleosome Remodeling." International Journal of Molecular Sciences 22, no. 4 (February 11, 2021): 1793. http://dx.doi.org/10.3390/ijms22041793.
Full textAbstract:
The Helicase-related protein 3 (Hrp3), an ATP-dependent chromatin remodeling enzyme from the CHD family, is crucial for maintaining global nucleosome occupancy in Schizosaccharomyces pombe (S. pombe). Although the ATPase domain of Hrp3 is essential for chromatin remodeling, the contribution of non-ATPase domains of Hrp3 is still unclear. Here, we investigated the role of non-ATPase domains using in vitro methods. In our study, we expressed and purified recombinant S. pombe histone proteins, reconstituted them into histone octamers, and assembled nucleosome core particles. Using reconstituted nucleosomes and affinity-purified wild type and mutant Hrp3 from S. pombe we created a homogeneous in vitro system to evaluate the ATP hydrolyzing capacity of truncated Hrp3 proteins. We found that all non-ATPase domain deletions (∆chromo, ∆SANT, ∆SLIDE, and ∆coupling region) lead to reduced ATP hydrolyzing activities in vitro with DNA or nucleosome substrates. Only the coupling region deletion showed moderate stimulation of ATPase activity with the nucleosome. Interestingly, affinity-purified Hrp3 showed co-purification with all core histones suggesting a strong association with the nucleosomes in vivo. However, affinity-purified Hrp3 mutant with SANT and coupling regions deletion showed complete loss of interactions with the nucleosomes, while SLIDE and chromodomain deletions reduced Hrp3 interactions with the nucleosomes. Taken together, nucleosome association and ATPase stimulation by DNA or nucleosomes substrate suggest that the enzymatic activity of Hrp3 is fine-tuned by unique contributions of all four non-catalytic domains.
39
Tanaka, M., J. D. Hennebold, J. Macfarlane, and E. Y. Adashi. "A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog." Development 128, no. 5 (March 1, 2001): 655–64. http://dx.doi.org/10.1242/dev.128.5.655.
Full textAbstract:
Oocytes and early embryos of multiple (non-mammalian) species lack the somatic form of the linker histone H1. To the best of our knowledge, a mammalian oocyte-specific linker (H1) histone(s) has not, as yet, been reported. We have uncovered the cDNA in question in the course of a differential screening (suppression subtractive hybridization (SSH)) project. Elucidation of the full-length sequence of this novel 1.2 kb cDNA led to the identification of a 912 bp open reading frame. The latter encoded a novel 34 kDa linker histone protein comprised of 304 amino acids, tentatively named H1oo. Amino acid BLAST analysis revealed that H1oo displayed the highest sequence homology to the oocyte-specific B4 histone of the frog, the respective central globular (putative DNA binding) domains displaying 54% identity. Substantial homology to the cs-H1 protein of the sea urchin oocyte was also apparent. While most oocytic mRNAs corresponding to somatic linker histones are not polyadenylated (and remain untranslated), the mRNAs of (non-mammalian) oocyte-specific linker histones and of mammalian H1oo, are polyadenylated, a process driven by the consensus signal sequence, AAUAAA, detected in the 3′-untranslated region of the H1oo cDNA. Our data suggest that the mouse oocyte-specific linker histone H1oo (1) constitutes a novel mammalian homolog of the oocyte-specific linker histone B4 of the frog and of the cs-H1 linker histone of the sea urchin; (2) is expressed as early as the GV (PI) stage oocyte, persisting into the MII stage oocyte, the oocytic polar bodies, and the two-cell embryo, extinction becoming apparent at the four- to eight-cell embryonic stage; and (3) may play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure.
40
Polyanichko, Alexander, and Helmut Wieser. "Structural organization of DNA–protein complexes of chromatin studied by vibrational and electronic circular dichroism." Spectroscopy 24, no. 3-4 (2010): 239–44. http://dx.doi.org/10.1155/2010/658374.
Full textAbstract:
Structure and functioning of chromatin is determined by interactions of DNA with numerous nuclear proteins. The most abundant and yet not completely understood non-histone chromosomal proteins are those belonging to a High Mobility Group (HMG) namely HMGB1. The interplay of this protein on DNA with linker histone H1 and other proteins determines both structure and functioning of the chromatin. A combination of UV and IR absorption and circular dichroism (CD) spectroscopy was applied to investigate the structure and formation of large supramolecular DNA–protein complexes. This combination of techniques was used to overcome limitations of UV-CD (ECD) spectroscopy due to considerable light scattering in such solutions. Based on the analysis of FTIR and UV circular dichroism spectra and AFM imaging the interaction of DNA with high-mobility group non-histone chromatin protein HMGB1 and linker histone H1 was studied.
41
Liaw, Patricia C. "Mediators of Disseminated Intravascular Coagulation: Molecular Mechanisms." Blood 130, Suppl_1 (December 7, 2017): SCI—2—SCI—2. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-2.sci-2.
Full textAbstract:
Abstract Disseminated intravascular coagulation (DIC) is characterized by a spectrum of haemorrhage and microvascular thrombosis complicating many conditions including sepsis and trauma. In recent years, there is growing evidence that damage associated molecular patterns (DAMPs) play a crucial role in the pathogenesis of DIC. Upon cell death and/or cell activation, extracellular DNA as well as DNA binding proteins (e.g. histones and high mobility group box 1 protein) are released into the circulation. These molecules can influence hemostasis by promoting coagulation via the contact pathway, inducing platelet aggregation, activating endothelial cells, and inhibiting fibrinolysis. Extracellular HMGB1 also activates neutrophils to induce the release of neutrophil extracellular traps, which may further contribute to tissue injury and organ dysfunction. Cell-free DNA (cfDNA) from nuclear, mitochondrial, and bacterial sources has varying pro-inflammatory effects, although all three have similar procoagulant and platelet-stimulating potential. Elevated levels of cfDNA and histones are predictive of poor outcome in sepsis and trauma, with neutrophils being the major source of DNA released from whole blood in vitro. In septic patients, endogenous cfDNA correlates positively with thrombin generation potential, and addition of recombinant DNase attenuates thrombin generation. In a cecal ligation and puncture (CLP) model of sepsis, plasma cfDNA levels rise within a few hours and are accompanied by elevations in IL-6 and thrombin-antithrombin complexes. Delayed (ie. 6 hours post-CLP surgery) but not early administration of recombinant DNase decreases bacterial load in the lungs, blood, and peritoneal cavity, and attenuates organ damage. Thus, the timing of DNase administration may be a crucial element in future investigations of the therapeutic potential of DNase in sepsis. With respect to potential therapeutic inhibitors of histones, activated protein C (APC) cleaves histones H2A, H3, and H4. Co-injection of APC with histones rescues mice from death. C-reactive protein (CRP) is an acute phase protein that reduces histone-induced endothelial cell damage and platelet aggregation. Administration of histones and CRP to mice reduces endothelial damage, alleviates thrombocytopenia, and attenuates coagulation activation. Heparin can also bind histones and prevent histone-mediated cytotoxicity of endothelial cells. In vivo, non-anticoagulant heparin reduces mortality from sterile inflammation and from sepsis in mouse models. Translational studies of septic patients have shown that the prognostic utility of clinical scores can be enhanced by combining it with cfDNA and protein C levels, suggesting that inclusion of cfDNA and protein C in risk stratification tools may be valuable for monitoring response to treatment, enhancing confidence in clinical decision making, or for inclusion in trials of new anti-sepsis therapies. In summary, cfDNA and DNA-binding proteins are critically involved in the pathogenesis of DIC. Strategies that inhibit or neutralize the harmful effects of cfDNA and histones may have great therapeutic potential. Disclosures No relevant conflicts of interest to declare.
42
Kee, Hae Jin, and Hyun Kook. "Roles and Targets of Class I and IIa Histone Deacetylases in Cardiac Hypertrophy." Journal of Biomedicine and Biotechnology 2011 (2011): 1–10. http://dx.doi.org/10.1155/2011/928326.
Full textAbstract:
Cardiac hypertrophy occurs in association with heart diseases and ultimately results in cardiac dysfunction and heart failure. Histone deacetylases (HDACs) are post-translational modifying enzymes that can deacetylate histones and non-histone proteins. Research with HDAC inhibitors has provided evidence that the class I HDACs are pro-hypertrophic. Among the class I HDACs, HDAC2 is activated by hypertrophic stresses in association with the induction of heat shock protein 70. Activated HDAC2 triggers hypertrophy by inhibiting the signal cascades of either Krüppel like factor 4 (KLF4) or inositol polyphosphate-5-phosphatase f (Inpp5f). Thus, modulators of HDAC2 enzymes, such as selective HDAC inhibitors, are considered to be an important target for heart diseases, especially for preventing cardiac hypertrophy. In contrast, class IIa HDACs have been shown to repress cardiac hypertrophy by inhibiting cardiac-specific transcription factors such as myocyte enhancer factor 2 (MEF2), GATA4, and NFAT in the heart. Studies of class IIa HDACs have shown that the underlying mechanism is regulated by nucleo-cytoplasm shuttling in response to a variety of stress signals. In this review, we focus on the class I and IIa HDACs that play critical roles in mediating cardiac hypertrophy and discuss the non-histone targets of HDACs in heart disease.
43
Kumar, Amish, and Gitanjali Yadav. "Diversification of the Histone Fold Motif in Plants: Evolution of New Functional Roles." Defence Life Science Journal 1, no. 1 (June 1, 2016): 63. http://dx.doi.org/10.14429/dlsj.1.10061.
Full textAbstract:
<p>The Histone fold motif (HFM) is one of the most conserved structural motifs in biology, mainly found in the core histone sub-units of all eukaryotes. The HFM represents a helix-strand-helix motif having three alpha helices connected by two loops/beta strands. This helix-strand-helix motif has the unique property of binding strongly with proteins as well as with DNA. Apart from core histones, the HFM has been reported in a variety of other proteins in all forms of life. In this work, we review the various classes of proteins that contain the HFM, as well as the diverse roles played by these proteins in the plant kingdom. As will be clear from this review, formation of the core histones through multi-merisation is not the only role played by this conserved fold, although the characteristic ability of the HFM to dimerize with suitable partner proteins has been used by nature to perform several non-core-histone functions. Most of the information about plant HFM containing proteins, such as identification and classification, has been done based on homology with yeast and animal counterparts. However, the ability of plants genomes to duplicate extensively has led to the existence of large gene families of the HFM containing proteins, unlike other eukaryotes. Plant HFM containing proteins can broadly be classified under the following major categories; TBP-associated factors (TAF), Nuclear Factor Y (NF-Y), Dr1/DrAp1 proteins and the chromatin accessibility complex (CHRAC). These proteins families are known to be involved in transcriptional regulation, co-activation and chromosome maintenance. Partner recognition through dimer formation remains a major conserved feature of these groups when compared with core histone sub-units.</p>
44
Kuhn, S., C. E. Vorgias, and P. Traub. "Interaction in vitro of non-epithelial intermediate filament proteins with supercoiled plasmid DNA." Journal of Cell Science 87, no. 4 (May 1, 1987): 543–54. http://dx.doi.org/10.1242/jcs.87.4.543.
Full textAbstract:
Sucrose gradient analysis of reaction products obtained from non-epithelial intermediate filament (IF) subunit proteins and a mixture of supercoiled, relaxed and linearized plasmid pBR322 DNA at low ionic strength revealed that limited amounts of these polypeptides interacted exclusively with the supercoiled form of the plasmid DNA. These results were corroborated by electron-microscopic analysis of the reaction products, which showed that only circles of supercoiled pBR322 DNA were completely and smoothly covered with vimentin. IFs reconstituted from pure vimentin reacted with supercoiled pBR322 DNA only through their physical ends. The reaction of an aged preparation of vimentin with supercoiled pBR322 DNA produced large aggregates consisting of a central, axially oriented protein scaffold to which individual loops of DNA were attached at their bases in a halo-like arrangement. The electron-microscopic appearance of such complexes was very reminiscent of that of histone-depleted metaphase chromosomes. Together with the previous observations that non-epithelial IF proteins have high affinities for single-stranded DNA and core histones and that they are structurally and functionally closely related to the nuclear lamins, these results were used to advance a novel hypothesis on the biological role of IF proteins in eukaryotic cells.
45
Lan, Fei, and Yang Shi. "Epigenetic regulation: methylation of histone and non-histone proteins." Science in China Series C: Life Sciences 52, no. 4 (April 2009): 311–22. http://dx.doi.org/10.1007/s11427-009-0054-z.
Full text
46
D’Mello, Santosh R. "Histone deacetylase-3: Friend and foe of the brain." Experimental Biology and Medicine 245, no. 13 (June 2, 2020): 1130–41. http://dx.doi.org/10.1177/1535370220928278.
Full textAbstract:
Histone deacetylases (HDACs) are a family of enzymes that deacetylate histones as well as a large number of other nuclear, cytoplasmic, and mitochondrial proteins. The deacetylation of histones transforms chromatin to a transcriptionally repressed state, whereas deacetylation of other cellular proteins regulates their functional activity through modulation of subcellular location, their interaction with other proteins, and in the case of transcription factors, their DNA-binding ability. A compelling body of evidence derived from the utilization of pharmacological inhibitors indicates that histone deacetylases are important regulators of brain development as well as the pathogenesis of neurodegenerative diseases. However, because most of the pharmacological inhibitors used are non-selective with regard to the different members of the HDAC family, the significance of individual HDAC proteins to brain development and degeneration has been difficult to delineate. This review focuses on HDAC3. Experiments conducted using more recently developed isoform selective inhibitors and molecular genetic approaches demonstrate that HDAC3 regulates different steps of neurodevelopment, including neurogenesis, gliogenesis, glial cell fate determination, and the myelination of oligodendrocytes and Schwann cells. However, specific posttranslational modifications and alterations in its binding partners transform HDAC3 from a protein that is beneficial to the brain to one that is neurotoxic. The role of HDAC3 in the promotion of neurodegeneration and the inhibition of recovery after nerve injury is reviewed. The role of HDAC3 in the regulation of memory in the adult and aging brain is also described. Impact statement Brain development and degeneration are highly complex processes that are regulated by a large number of molecules and signaling pathways the identities of which are being unraveled. Accumulating evidence points to histone deacetylases and epigenetic mechanisms as being important regulators of these processes. In this review, we describe that histone deacetylase-3 (HDAC3) is a particularly crucial regulator of both neurodevelopment and neurodegeneration. In addition, HDAC3 regulates memory formation, synaptic plasticity, and the cognitive impairment associated with normal aging. Understanding how HDAC3 functions contributes to the normal development and functioning of the brain while also promoting neurodegeneration could lead to the development of therapeutic approaches for neurodevelopmental, neuropsychiatric, and neurodegenerative disorders.
47
Imai, Yoichi, Mitsuhito Hirano, Masayuki Kobayashi, Muneyoshi Futami, and Arinobu Tojo. "HDAC Inhibitors Exert Anti-Myeloma Effects through Multiple Modes of Action." Cancers 11, no. 4 (April 4, 2019): 475. http://dx.doi.org/10.3390/cancers11040475.
Full textAbstract:
HDACs are critical regulators of gene expression that function through histone modification. Non-histone proteins and histones are targeted by these proteins and the inhibition of HDACs results in various biological effects. Moreover, the aberrant expression and function of these proteins is thought to be related to the pathogenesis of multiple myeloma (MM) and several inhibitors have been introduced or clinically tested. Panobinostat, a pan-HDAC inhibitor, in combination with a proteasome inhibitor and dexamethasone has improved survival in relapsing/refractory MM patients. We revealed that panobinostat inhibits MM cell growth by degrading the protein PPP3CA, a catalytic subunit of calcineurin. This degradation was suggested to be mediated by suppression of the chaperone function of HSP90 due to HDAC6 inhibition. Cytotoxicity due to the epigenetic regulation of tumor-associated genes by HDAC inhibitors has also been reported. In addition, HDAC6 inhibition enhances tumor immunity and has been suggested to strengthen the cytotoxic effects of therapeutic antibodies against myeloma. Furthermore, therapeutic strategies to enhance the anti-myeloma effects of HDAC inhibitors through the addition of other agents has been intensely evaluated. Thus, the treatment of patients with MM using HDAC inhibitors is promising as these drugs exert their effects through multiple modes of action.
48
Hard, Ryan, Nan Li, Wei He, Brian Ross, Gary C. H. Mo, Qin Peng, Richard S. L. Stein, et al. "Deciphering and engineering chromodomain-methyllysine peptide recognition." Science Advances 4, no. 11 (November 2018): eaau1447. http://dx.doi.org/10.1126/sciadv.aau1447.
Full textAbstract:
Posttranslational modifications (PTMs) play critical roles in regulating protein functions and mediating protein-protein interactions. An important PTM is lysine methylation that orchestrates chromatin modifications and regulates functions of non-histone proteins. Methyllysine peptides are bound by modular domains, of which chromodomains are representative. Here, we conducted the first large-scale study of chromodomains in the human proteome interacting with both histone and non-histone methyllysine peptides. We observed significant degenerate binding between chromodomains and histone peptides, i.e., different histone sites can be recognized by the same set of chromodomains, and different chromodomains can share similar binding profiles to individual histone sites. Such degenerate binding is not dictated by amino acid sequence or PTM motif but rather rooted in the physiochemical properties defined by the PTMs on the histone peptides. This molecular mechanism is confirmed by the accurate prediction of the binding specificity using a computational model that captures the structural and energetic patterns of the domain-peptide interaction. To further illustrate the power and accuracy of our model, we used it to effectively engineer an exceptionally strong H3K9me3-binding chromodomain and to label H3K9me3 in live cells. This study presents a systematic approach to deciphering domain-peptide recognition and reveals a general principle by which histone modifications are interpreted by reader proteins, leading to dynamic regulation of gene expression and other biological processes.
49
Chioccarelli, Teresa, Riccardo Pierantoni, Francesco Manfrevola, Veronica Porreca, Silvia Fasano, Rosanna Chianese, and Gilda Cobellis. "Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality." Journal of Clinical Medicine 9, no. 3 (February 27, 2020): 640. http://dx.doi.org/10.3390/jcm9030640.
Full textAbstract:
Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of spermatogonia (SPG), meiotic recombination, nuclear condensation in spermatids (SPT). Nuclear condensation is related to chromatin remodeling events and requires a massive histone-to-protamine exchange. After this event a small percentage of chromatin is condensed by histones and SPZ contain nucleoprotamines and a small fraction of nucleohistone chromatin carrying a landascape of histone PTMs. Circular RNAs (circRNAs), a new class of non-coding RNAs, characterized by a nonlinear back-spliced junction, able to play as microRNA (miRNA) sponges, protein scaffolds and translation templates, have been recently characterized in both human and mouse SPZ. Since their abundance in eukaryote tissues, it is challenging to deepen their biological function, especially in the field of reproduction. Here we review the critical role of histone PTMs in male germ cells and the profile of circRNAs in mouse and human SPZ. Furthermore, we discuss their suggested role as novel epigenetic biomarkers to assess sperm quality and improve artificial insemination procedure.
50
Kassner, Ingrid, Anneli Andersson, Monika Fey, Martin Tomas, Elisa Ferrando-May, and Michael O. Hottiger. "SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress." Open Biology 3, no. 10 (October 2013): 120173. http://dx.doi.org/10.1098/rsob.120173.
Full textAbstract:
ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.