Journal articles: 'Genome Compaction'

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Cabrera, Julio E., Cedric Cagliero, Selwyn Quan, Catherine L. Squires, and Ding Jun Jin. "Active Transcription of rRNA Operons Condenses the Nucleoid in Escherichia coli: Examining the Effect of Transcription on Nucleoid Structure in the Absence of Transertion." Journal of Bacteriology 191, no. 13 (April 24, 2009): 4180–85. http://dx.doi.org/10.1128/jb.01707-08.

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ABSTRACT In Escherichia coli the genome must be compacted ∼1,000-fold to be contained in a cellular structure termed the nucleoid. It is proposed that the structure of the nucleoid is determined by a balance of multiple compaction forces and one major expansion force. The latter is mediated by transertion, a coupling of transcription, translation, and translocation of nascent membrane proteins and/or exported proteins. In supporting this notion, it has been shown consistently that inhibition of transertion by the translation inhibitor chloramphenicol results in nucleoid condensation due to the compaction forces that remain active in the cell. Our previous study showed that during optimal growth, RNA polymerase is concentrated into transcription foci or “factories,” analogous to the eukaryotic nucleolus, indicating that transcription and RNA polymerase distribution affect the nucleoid structure. However, the interpretation of the role of transcription in the structure of the nucleoid is complicated by the fact that transcription is implicated in both compacting forces and the expansion force. In this work, we used a new approach to further examine the effect of transcription, specifically from rRNA operons, on the structure of the nucleoid, when the major expansion force was eliminated. Our results showed that transcription is necessary for the chloramphenicol-induced nucleoid compaction. Further, an active transcription from multiple rRNA operons in chromosome is critical for the compaction of nucleoid induced by inhibition of translation. All together, our data demonstrated that transcription of rRNA operons is a key mechanism affecting genome compaction and nucleoid structure.

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McLysaght, Aoife, Anton J. Enright, Lucy Skrabanek, and Kenneth H. Wolfe. "Estimation of Synteny Conservation and Genome Compaction Between Pufferfish (Fugu) and Human." Yeast 1, no. 1 (2000): 22–36. http://dx.doi.org/10.1002/(sici)1097-0061(200004)17:1<22::aid-yea5>3.0.co;2-s.

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Background: Knowledge of the amount of gene order and synteny conservation between two species gives insights to the extent and mechanisms of divergence. The vertebrateFugu rubripes(pufferfish) has a small genome with little repetitive sequence which makes it attractive as a model genome. Genome compaction and synteny conservation between human andFuguwere studied using data from public databases.Methods: Intron length and map positions of human andFuguorthologues were compared to analyse relative genome compaction and synteny conservation respectivley. The divergence of these two genomes by genome rearrangement was simulated and the results were compared to the real data.Results: Analysis of 199 introns in 22 orthologous genes showed an eight-fold average size reduction inFugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours inFugu(genes from the same cosmid or GenBank entry), 40–50% have conserved synteny with a human chromosome. This figure may be underestimated by as much as two-fold, due to problems caused by incomplete human genome sequence data and the existence of dispersed gene families. Some genes that are neighbours inFuguhave human orthologues that are several megabases and tens of genes apart. This is probably caused by small inversions or other intrachromosomal rearrangements.Conclusions: Comparison of observed data to computer simulations suggests that 4000–16 000 chromosomal rearrangements have occured sinceFuguand human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons.

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Slamovits, Claudio H., Naomi M. Fast, Joyce S. Law, and Patrick J. Keeling. "Genome Compaction and Stability in Microsporidian Intracellular Parasites." Current Biology 14, no. 10 (May 2004): 891–96. http://dx.doi.org/10.1016/j.cub.2004.04.041.

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McLysaght, Aoife, Anton J. Enright, Lucy Skrabanek, and Kenneth H. Wolfe. "Estimation of Synteny Conservation and Genome Compaction Between Pufferfish (Fugu) and Human." Yeast 1, no. 1 (January 1, 2000): 22–36. http://dx.doi.org/10.1155/2000/234298.

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Background: Knowledge of the amount of gene order and synteny conservation between two species gives insights to the extent and mechanisms of divergence. The vertebrate Fugu rubripes (pufferfish) has a small genome with little repetitive sequence which makes it attractive as a model genome. Genome compaction and synteny conservation between human and Fugu were studied using data from public databases.Methods: Intron length and map positions of human and Fugu orthologues were compared to analyse relative genome compaction and synteny conservation respectivley. The divergence of these two genomes by genome rearrangement was simulated and the results were compared to the real data.Results: Analysis of 199 introns in 22 orthologous genes showed an eight-fold average size reduction in Fugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours in Fugu (genes from the same cosmid or GenBank entry), 40–50% have conserved synteny with a human chromosome. This figure may be underestimated by as much as two-fold, due to problems caused by incomplete human genome sequence data and the existence of dispersed gene families. Some genes that are neighbours in Fugu have human orthologues that are several megabases and tens of genes apart. This is probably caused by small inversions or other intrachromosomal rearrangements.Conclusions: Comparison of observed data to computer simulations suggests that 4000–16 000 chromosomal rearrangements have occured since Fugu and human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons.

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Brahmachari, Sumitabha, and John F. Marko. "Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures." Proceedings of the National Academy of Sciences 116, no. 50 (November 22, 2019): 24956–65. http://dx.doi.org/10.1073/pnas.1906355116.

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Eukaryote cell division features a chromosome compaction–decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compaction-segregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops—a polymer “brush”—where active extrusion of loops controls the brush structure. Given type-II DNA topoisomerase (Topo II)-catalyzed topology fluctuations, we find that interchromosome entanglements are minimized for a certain “optimal” loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle and highlights a mechanism of directing Topo II-mediated strand passage via loop extrusion-driven lengthwise compaction.

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Kaufman, Brett A., Nela Durisic, Jeffrey M. Mativetsky, Santiago Costantino, Mark A. Hancock, Peter Grutter, and Eric A. Shoubridge. "The Mitochondrial Transcription Factor TFAM Coordinates the Assembly of Multiple DNA Molecules into Nucleoid-like Structures." Molecular Biology of the Cell 18, no. 9 (September 2007): 3225–36. http://dx.doi.org/10.1091/mbc.e07-05-0404.

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Packaging DNA into condensed structures is integral to the transmission of genomes. The mammalian mitochondrial genome (mtDNA) is a high copy, maternally inherited genome in which mutations cause a variety of multisystem disorders. In all eukaryotic cells, multiple mtDNAs are packaged with protein into spheroid bodies called nucleoids, which are the fundamental units of mtDNA segregation. The mechanism of nucleoid formation, however, remains unknown. Here, we show that the mitochondrial transcription factor TFAM, an abundant and highly conserved High Mobility Group box protein, binds DNA cooperatively with nanomolar affinity as a homodimer and that it is capable of coordinating and fully compacting several DNA molecules together to form spheroid structures. We use noncontact atomic force microscopy, which achieves near cryo-electron microscope resolution, to reveal the structural details of protein–DNA compaction intermediates. The formation of these complexes involves the bending of the DNA backbone, and DNA loop formation, followed by the filling in of proximal available DNA sites until the DNA is compacted. These results indicate that TFAM alone is sufficient to organize mitochondrial chromatin and provide a mechanism for nucleoid formation.

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Guttula, Durgarao, Fan Liu, Jeroen A. van Kan, Véronique Arluison, and Johan R. C. van der Maarel. "Effect of HU protein on the conformation and compaction of DNA in a nanochannel." Soft Matter 14, no. 12 (2018): 2322–28. http://dx.doi.org/10.1039/c7sm02118f.

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Jiang, Kai, Nicolas Humbert, Sriram K.K., Ioulia Rouzina, Yves Mely, and Fredrik Westerlund. "The HIV-1 nucleocapsid chaperone protein forms locally compacted globules on long double-stranded DNA." Nucleic Acids Research 49, no. 8 (April 19, 2021): 4550–63. http://dx.doi.org/10.1093/nar/gkab236.

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Abstract The nucleocapsid (NC) protein plays key roles in Human Immunodeficiency Virus 1 (HIV-1) replication, notably by condensing and protecting the viral RNA genome and by chaperoning its reverse transcription into double-stranded DNA (dsDNA). Recent findings suggest that integration of viral dsDNA into the host genome, and hence productive infection, is linked to a small subpopulation of viral complexes where reverse transcription was completed within the intact capsid. Therefore, the synthesized dsDNA has to be tightly compacted, most likely by NC, to prevent breaking of the capsid in these complexes. To investigate NC’s ability to compact viral dsDNA, we here characterize the compaction of single dsDNA molecules under unsaturated NC binding conditions using nanofluidic channels. Compaction is shown to result from accumulation of NC at one or few compaction sites, which leads to small dsDNA condensates. NC preferentially initiates compaction at flexible regions along the dsDNA, such as AT-rich regions and DNA ends. Upon further NC binding, these condensates develop into a globular state containing the whole dsDNA molecule. These findings support NC’s role in viral dsDNA compaction within the mature HIV-1 capsid and suggest a possible scenario for the gradual dsDNA decondensation upon capsid uncoating and NC loss.

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Kwon, Sunyoung, Byunghan Lee, Seunghyun Park, Jeonghee Jo, and Sungroh Yoon. "The Analysis of Genome Database Compaction based on Sequence Similarity." KIISE Transactions on Computing Practices 23, no. 4 (April 15, 2017): 250–55. http://dx.doi.org/10.5626/ktcp.2017.23.4.250.

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Machín, Félix, Jordi Torres-Rosell, Adam Jarmuz, and Luis Aragón. "Spindle-independent condensation-mediated segregation of yeast ribosomal DNA in late anaphase." Journal of Cell Biology 168, no. 2 (January 17, 2005): 209–19. http://dx.doi.org/10.1083/jcb.200408087.

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Mitotic cell division involves the equal segregation of all chromosomes during anaphase. The presence of ribosomal DNA (rDNA) repeats on the right arm of chromosome XII makes it the longest in the budding yeast genome. Previously, we identified a stage during yeast anaphase when rDNA is stretched across the mother and daughter cells. Here, we show that resolution of sister rDNAs is achieved by unzipping of the locus from its centromere-proximal to centromere-distal regions. We then demonstrate that during this stretched stage sister rDNA arrays are neither compacted nor segregated despite being largely resolved from each other. Surprisingly, we find that rDNA segregation after this period no longer requires spindles but instead involves Cdc14-dependent rDNA axial compaction. These results demonstrate that chromosome resolution is not simply a consequence of compacting chromosome arms and that overall rDNA compaction is necessary to mediate the segregation of the long arm of chromosome XII.

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Bian, Qian, Erika C. Anderson, Qiming Yang, and Barbara J. Meyer. "Histone H3K9 methylation promotes formation of genome compartments inCaenorhabditis elegansvia chromosome compaction and perinuclear anchoring." Proceedings of the National Academy of Sciences 117, no. 21 (May 8, 2020): 11459–70. http://dx.doi.org/10.1073/pnas.2002068117.

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Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization inCaenorhabditis elegansand investigate roles for compartments in regulating gene expression. Distal arms ofC. eleganschromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other bothin cisandin trans,while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genesmet-2andset-25significantly impaired formation of inactive Arm and active Center compartments.cec-4mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote theircisassociation, and an anchoring-independent mechanism that compacts individual chromosome arms. In bothmet-2 set-25andcec-4mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

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Ražná, Katarína, Vladimír Rataj, Miroslav Macák, and Jana Galambošová. "MicroRNA-based markers as a tool to monitor the barley (Hordeum vulgare L.) response to soil compaction." Acta fytotechnica et zootechnica 23, no. 3 (September 30, 2020): 139–46. http://dx.doi.org/10.15414/afz.2020.23.03.139-146.

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Plants are often exposed to adverse environmental conditions that can significantly interfere with their genomic response. Soil compaction induced by heavy field machinery represents a major problem for crop production mainly due to restricted root growth and penetration into soil and therefore reduced water and nutrient uptake by the plants. Tested hypotheses were to declare whether the plant‘s genome responds to soil compaction and whether the microRNA-based markers are suitable to determine this response. A long term field scale experiment was established in 2009 where different levels of soil compaction are researched from the soil and crop point of view. The analyzed barley (Hordeum vulgare L.) plants were collected during the growing season in 2019. The effect of soil compaction was analysed by four different DNA-based markers corresponding to miRNA sequences of dehydratation stress-responsive barley miRNAs (hvu-miR156, and hvu-miR408) and nutrition-sensitive markers (hvu-miR399 and hvu-miR827), within the leaf, stem and root tissues of barley plants. Our preliminary data support hypotheses that plant genome response was tissue-specific due to significant induction of the biomarkers to dehydratation and nutrition stress. The most affected part of the plant by dehydration, were roots and lack of nutrient supply was most pronounced on leaves.

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Ishihara, Satoru, Yohei Sasagawa, Takeru Kameda, Hayato Yamashita, Mana Umeda, Naoe Kotomura, Masayuki Abe, Yohei Shimono, and Itoshi Nikaido. "Local states of chromatin compaction at transcription start sites control transcription levels." Nucleic Acids Research 49, no. 14 (July 7, 2021): 8007–23. http://dx.doi.org/10.1093/nar/gkab587.

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Abstract The ‘open’ and ‘compact’ regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone H1 was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that H1 bound to H3 interacts with another H1 in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.

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Katinka, Michaël D., Simone Duprat, Emmanuel Cornillot, Guy Méténier, Fabienne Thomarat, Gérard Prensier, Valérie Barbe, et al. "Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi." Nature 414, no. 6862 (November 2001): 450–53. http://dx.doi.org/10.1038/35106579.

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Kim, Yoori, Zhubing Shi, Hongshan Zhang, Ilya J. Finkelstein, and Hongtao Yu. "Human cohesin compacts DNA by loop extrusion." Science 366, no. 6471 (November 28, 2019): 1345–49. http://dx.doi.org/10.1126/science.aaz4475.

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Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence is lacking. Here, we used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. Our results establish cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion.

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Bellush, James M., and Iestyn Whitehouse. "DNA replication through a chromatin environment." Philosophical Transactions of the Royal Society B: Biological Sciences 372, no. 1731 (August 28, 2017): 20160287. http://dx.doi.org/10.1098/rstb.2016.0287.

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Compaction of the genome into the nuclear space is achieved by wrapping DNA around octameric assemblies of histone proteins to form nucleosomes, the fundamental repeating unit of chromatin. Aside from providing a means by which to fit larger genomes into the cell, chromatinization of DNA is a crucial means by which the cell regulates access to the genome. While the complex role that chromatin plays in gene transcription has been appreciated for a long time, it is now also apparent that crucial aspects of DNA replication are linked to the biology of chromatin. This review will focus on recent advances in our understanding of how the chromatin environment influences key aspects of DNA replication. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling'.

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Xiao, Botao, Benjamin S. Freedman, Kelly E. Miller, Rebecca Heald, and John F. Marko. "Histone H1 compacts DNA under force and during chromatin assembly." Molecular Biology of the Cell 23, no. 24 (December 15, 2012): 4864–71. http://dx.doi.org/10.1091/mbc.e12-07-0518.

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Histone H1 binds to linker DNA between nucleosomes, but the dynamics and biological ramifications of this interaction remain poorly understood. We performed single-molecule experiments using magnetic tweezers to determine the effects of H1 on naked DNA in buffer or during chromatin assembly in Xenopus egg extracts. In buffer, nanomolar concentrations of H1 induce bending and looping of naked DNA at stretching forces below 0.6 pN, effects that can be reversed with 2.7-pN force or in 200 mM monovalent salt concentrations. Consecutive tens-of-nanometer bending events suggest that H1 binds to naked DNA in buffer at high stoichiometries. In egg extracts, single DNA molecules assemble into nucleosomes and undergo rapid compaction. Histone H1 at endogenous physiological concentrations increases the DNA compaction rate during chromatin assembly under 2-pN force and decreases it during disassembly under 5-pN force. In egg cytoplasm, histone H1 protects sperm nuclei undergoing genome-wide decondensation and chromatin assembly from becoming abnormally stretched or fragmented due to astral microtubule pulling forces. These results reveal functional ramifications of H1 binding to DNA at the single-molecule level and suggest an important physiological role for H1 in compacting DNA under force and during chromatin assembly.

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Keeling, Patrick J. "Reduction and Compaction in the Genome of the Apicomplexan Parasite Cryptosporidium parvum." Developmental Cell 6, no. 5 (May 2004): 614–16. http://dx.doi.org/10.1016/s1534-5807(04)00135-2.

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Khurana, Simran, Michael J. Kruhlak, Jeongkyu Kim, Andy D. Tran, Jinping Liu, Katherine Nyswaner, Lei Shi, et al. "A Macrohistone Variant Links Dynamic Chromatin Compaction to BRCA1-Dependent Genome Maintenance." Cell Reports 8, no. 4 (August 2014): 1049–62. http://dx.doi.org/10.1016/j.celrep.2014.07.024.

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Khan, Jamshed, and Rob Patro. "Cuttlefish: fast, parallel and low-memory compaction of de Bruijn graphs from large-scale genome collections." Bioinformatics 37, Supplement_1 (July 1, 2021): i177—i186. http://dx.doi.org/10.1093/bioinformatics/btab309.

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Abstract Motivation The construction of the compacted de Bruijn graph from collections of reference genomes is a task of increasing interest in genomic analyses. These graphs are increasingly used as sequence indices for short- and long-read alignment. Also, as we sequence and assemble a greater diversity of genomes, the colored compacted de Bruijn graph is being used more and more as the basis for efficient methods to perform comparative genomic analyses on these genomes. Therefore, time- and memory-efficient construction of the graph from reference sequences is an important problem. Results We introduce a new algorithm, implemented in the tool Cuttlefish, to construct the (colored) compacted de Bruijn graph from a collection of one or more genome references. Cuttlefish introduces a novel approach of modeling de Bruijn graph vertices as finite-state automata, and constrains these automata’s state-space to enable tracking their transitioning states with very low memory usage. Cuttlefish is also fast and highly parallelizable. Experimental results demonstrate that it scales much better than existing approaches, especially as the number and the scale of the input references grow. On a typical shared-memory machine, Cuttlefish constructed the graph for 100 human genomes in under 9 h, using ∼29 GB of memory. On 11 diverse conifer plant genomes, the compacted graph was constructed by Cuttlefish in under 9 h, using ∼84 GB of memory. The only other tool completing these tasks on the hardware took over 23 h using ∼126 GB of memory, and over 16 h using ∼289 GB of memory, respectively. Availability and implementation Cuttlefish is implemented in C++14, and is available under an open source license at https://github.com/COMBINE-lab/cuttlefish. Supplementary information Supplementary data are available at Bioinformatics online.

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Liu, Bin, Siwei Chen, Anouk La Rose, Deng Chen, Fangyuan Cao, Martijn Zwinderman, Dominik Kiemel, Manon Aïssi, Frank J. Dekker, and Hidde J. Haisma. "Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing." Nucleic Acids Research 48, no. 2 (December 4, 2019): 517–32. http://dx.doi.org/10.1093/nar/gkz1136.

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Abstract Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1–9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.

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Johnson, J., C. A. Brackley, P. R. Cook, and D. Marenduzzo. "A simple model for DNA bridging proteins and bacterial or human genomes: bridging-induced attraction and genome compaction." Journal of Physics: Condensed Matter 27, no. 6 (January 7, 2015): 064119. http://dx.doi.org/10.1088/0953-8984/27/6/064119.

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Hoencamp, Claire, Olga Dudchenko, Ahmed M. O. Elbatsh, Sumitabha Brahmachari, Jonne A. Raaijmakers, Tom van Schaik, Ángela Sedeño Cacciatore, et al. "3D genomics across the tree of life reveals condensin II as a determinant of architecture type." Science 372, no. 6545 (May 27, 2021): 984–89. http://dx.doi.org/10.1126/science.abe2218.

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We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.

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POULIN, ROBERT, and HASEEB S. RANDHAWA. "Evolution of parasitism along convergent lines: from ecology to genomics." Parasitology 142, S1 (November 11, 2013): S6—S15. http://dx.doi.org/10.1017/s0031182013001674.

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SUMMARYFrom hundreds of independent transitions from a free-living existence to a parasitic mode of life, separate parasite lineages have converged over evolutionary time to share traits and exploit their hosts in similar ways. Here, we first summarize the evidence that, at a phenotypic level, eukaryotic parasite lineages have all converged toward only six general parasitic strategies: parasitoid, parasitic castrator, directly transmitted parasite, trophically transmitted parasite, vector-transmitted parasite or micropredator. We argue that these strategies represent adaptive peaks, with the similarities among unrelated taxa within any strategy extending to all basic aspects of host exploitation and transmission among hosts and transcending phylogenetic boundaries. Then, we extend our examination of convergent patterns by looking at the evolution of parasite genomes. Despite the limited taxonomic coverage of sequenced parasite genomes currently available, we find some evidence of parallel evolution among unrelated parasite taxa with respect to genome reduction or compaction, and gene losses or gains. Matching such changes in parasite genomes with the broad phenotypic traits that define the convergence of parasites toward only six strategies of host exploitation is not possible at present. Nevertheless, as more parasite genomes become available, we may be able to detect clear trends in the evolution of parasitic genome architectures representing true convergent adaptive peaks, the genomic equivalents of the phenotypic strategies used by all parasites.

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Sidorenko, D. S., T. Yu Zykova, V. A. Khoroshko, G. V. Pokholkova, S. A. Demakov, J. Larsson, E. S. Belyaeva, and I. F. Zhimulev. "Polytene chromosomes reflect functional organization of the Drosophila genome." Vavilov Journal of Genetics and Breeding 23, no. 2 (March 30, 2019): 148–53. http://dx.doi.org/10.18699/vj19.474.

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Polytene chromosomes of Drosophila melanogaster are a convenient model for studying interphase chromosomes of eukaryotes. They are giant in size in comparison with diploid cell chromosomes and have a pattern of cross stripes resulting from the ordered chromatid arrangement. Each region of polytene chromosomes has a unique banding pattern. Using the model of four chromatin types that reveals domains of varying compaction degrees, we were able to correlate the physical and cytological maps of some polytene chromosome regions and to show the main properties of genetic and molecular organization of bands and interbands, that we describe in this review. On the molecular map of the genome, the interbands correspond to decompacted aquamarine chromatin and 5’ ends of ubiquitously active genes. Gray bands contain lazurite and malachite chromatin, intermediate in the level of compaction, and, mainly, coding parts of genes. Dense black transcriptionally inactive bands are enriched in ruby chromatin. Localization of several dozens of interbands on the genome molecular map allowed us to study in detail their architecture according to the data of whole genome projects. The distribution of proteins and regulatory elements of the genome in the promoter regions of genes localized in the interbands shows that these parts of interbands are probably responsible for the formation of open chromatin that is visualized in polytene chromosomes as interbands. Thus, the permanent genetic activity of interbands and gray bands and the inactivity of genes in black bands are the basis of the universal banding pattern in the chromosomes of all Drosophila tissues. The smallest fourth chromosome of Drosophila with an atypical protein composition of chromatin is a special case. Using the model of four chromatin states and fluorescent in situ hybridization, its cytological map was refined and the genomic coordinates of all bands and interbands were determined. It was shown that, in spite of the peculiarities of this chromosome, its band organization in general corresponds to the rest of the genome. Extremely long genes of different Drosophila chromosomes do not fit the common scheme, since they can occupy a series of alternating bands and interbands (up to nine chromosomal structures) formed by parts of these genes.

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Nguyen, Lim, and Yokota. "Genome Editing for the Understanding and Treatment of Inherited Cardiomyopathies." International Journal of Molecular Sciences 21, no. 3 (January 22, 2020): 733. http://dx.doi.org/10.3390/ijms21030733.

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Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

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Haag, K. L., T. Y. James, J. F. Pombert, R. Larsson, T. M. M. Schaer, D. Refardt, and D. Ebert. "Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites." Proceedings of the National Academy of Sciences 111, no. 43 (October 13, 2014): 15480–85. http://dx.doi.org/10.1073/pnas.1410442111.

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Martin, Karen L., and Henry J. Leese. "Role of developmental factors in the switch from pyruvate to glucose as the major exogenous energy substrate in the preimplantation mouse embryo." Reproduction, Fertility and Development 11, no. 8 (1999): 425. http://dx.doi.org/10.1071/rd97071.

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Preimplantation mouse embryos, cultured in vitro and those freshly flushed from the reproductive tract, exhibit a switch in energy substrate preference, from pyruvate during the early preimplantation stages, to glucose at the blastocyst stage. Although the biochemical basis of this phenomenon is quite well characterized, its timing and possible association with developmental factors have not been considered. We have therefore examined the role of five developmental factors in determining the timing of the switch, namely: (1) embryo age (in hours post hCG); (2) developmental stage; (3) cytokinesis; (4) cell number; and (5) activation of the embryonic genome. One-cell embryos, which develop more slowly than 2-cell embryos in vitro, were used to investigate the role of embryo age and developmental stage. Cytochalasin D, which inhibits cytokinesis and delays the timing of compaction and cavitation, was used to investigate the role of cell division and developmental stage. Finally, transcription of the embryonic genome was examined with the inhibitor, α-amanitin. Pyruvate and glucose consumption by single embryos were measured using a non-invasive ultramicrofluorometric technique. The results showed that the timing of the switch in energy substrate preference is precisely regulated in the mouse preimplantation embryo. Activation of the embryonic genome is a prerequisite for the switch and its timing is closely associated with developmental stage, specifically compaction and/or cavitation. Cell number, cytokinesis and embryo age appeared to be unrelated to the timing of the switch. These conclusions may well be extrapolated to other species, since an increase in net glucose uptake, if not always at the expense of pyruvate, is a feature of preimplantation embryo metabolism in all mammals studied.

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van der Heijden, Thijn, Joke J. F. A. van Vugt, Colin Logie, and John van Noort. "Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy." Proceedings of the National Academy of Sciences 109, no. 38 (August 20, 2012): E2514—E2522. http://dx.doi.org/10.1073/pnas.1205659109.

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Nucleosome positioning dictates eukaryotic DNA compaction and access. To predict nucleosome positions in a statistical mechanics model, we exploited the knowledge that nucleosomes favor DNA sequences with specific periodically occurring dinucleotides. Our model is the first to capture both dyad position within a few base pairs, and free binding energy within 2 kBT, for all the known nucleosome positioning sequences. By applying Percus’s equation to the derived energy landscape, we isolate sequence effects on genome-wide nucleosome occupancy from other factors that may influence nucleosome positioning. For both in vitro and in vivo systems, three parameters suffice to predict nucleosome occupancy with correlation coefficients of respectively 0.74 and 0.66. As predicted, we find the largest deviations in vivo around transcription start sites. This relatively simple algorithm can be used to guide future studies on the influence of DNA sequence on chromatin organization.

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Villanueva, Rodrigo A., José L. Galaz, Juan A. Valdés, Matilde M. Jashés, and Ana María Sandino. "Genome Assembly and Particle Maturation of the Birnavirus Infectious Pancreatic Necrosis Virus." Journal of Virology 78, no. 24 (December 15, 2004): 13829–38. http://dx.doi.org/10.1128/jvi.78.24.13829-13838.2004.

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ABSTRACT In this study, we have analyzed the morphogenesis of the birnavirus infectious pancreatic necrosis virus throughout the infective cycle in CHSE-214 cells by using a native agarose electrophoresis system. Two types of viral particles (designated A and B) were identified, isolated, and characterized both molecularly and biologically. Together, our results are consistent with a model of morphogenesis in which the genomic double-stranded RNA is immediately assembled, after synthesis, into a large (66-nm diameter) and uninfectious particle A, where the capsid is composed of both mature and immature viral polypeptides. Upon maturation, particles A yield particles B through the proteolytic cleavage of most of the remaining viral precursors within the capsid, the compaction of the particle (60-nm diameter), and the acquisition of infectivity. These studies will provide the foundation for further analyses of birnavirus particle assembly and RNA replication.

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Walther, Nike, M. Julius Hossain, Antonio Z. Politi, Birgit Koch, Moritz Kueblbeck, Øyvind Ødegård-Fougner, Marko Lampe, and Jan Ellenberg. "A quantitative map of human Condensins provides new insights into mitotic chromosome architecture." Journal of Cell Biology 217, no. 7 (April 9, 2018): 2309–28. http://dx.doi.org/10.1083/jcb.201801048.

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The two Condensin complexes in human cells are essential for mitotic chromosome structure. We used homozygous genome editing to fluorescently tag Condensin I and II subunits and mapped their absolute abundance, spacing, and dynamic localization during mitosis by fluorescence correlation spectroscopy (FSC)–calibrated live-cell imaging and superresolution microscopy. Although ∼35,000 Condensin II complexes are stably bound to chromosomes throughout mitosis, ∼195,000 Condensin I complexes dynamically bind in two steps: prometaphase and early anaphase. The two Condensins rarely colocalize at the chromatid axis, where Condensin II is centrally confined, but Condensin I reaches ∼50% of the chromatid diameter from its center. Based on our comprehensive quantitative data, we propose a three-step hierarchical loop model of mitotic chromosome compaction: Condensin II initially fixes loops of a maximum size of ∼450 kb at the chromatid axis, whose size is then reduced by Condensin I binding to ∼90 kb in prometaphase and ∼70 kb in anaphase, achieving maximum chromosome compaction upon sister chromatid segregation.

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Murga, Matilde, Isabel Jaco, Yuhong Fan, Rebeca Soria, Barbara Martinez-Pastor, Myriam Cuadrado, Seung-Min Yang, Maria A. Blasco, Arthur I. Skoultchi, and Oscar Fernandez-Capetillo. "Global chromatin compaction limits the strength of the DNA damage response." Journal of Cell Biology 178, no. 7 (September 24, 2007): 1101–8. http://dx.doi.org/10.1083/jcb.200704140.

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In response to DNA damage, chromatin undergoes a global decondensation process that has been proposed to facilitate genome surveillance. However, the impact that chromatin compaction has on the DNA damage response (DDR) has not directly been tested and thus remains speculative. We apply two independent approaches (one based on murine embryonic stem cells with reduced amounts of the linker histone H1 and the second making use of histone deacetylase inhibitors) to show that the strength of the DDR is amplified in the context of “open” chromatin. H1-depleted cells are hyperresistant to DNA damage and present hypersensitive checkpoints, phenotypes that we show are explained by an increase in the amount of signaling generated at each DNA break. Furthermore, the decrease in H1 leads to a general increase in telomere length, an as of yet unrecognized role for H1 in the regulation of chromosome structure. We propose that slight differences in the epigenetic configuration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks.

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Schwartz (Berkaeva), M. B., T. E. Pankova, and S. A. Demakov. "ADF1 and BEAF-32 chromatin proteins affect nucleosome positioning and DNA decompaction in 61C7/C8 interband region of Drosophila melanogaster polytene chromosomes." Vavilov Journal of Genetics and Breeding 23, no. 2 (March 30, 2019): 154–59. http://dx.doi.org/10.18699/vj19.475.

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The formation of interphase chromosomes is a multi-level process in which DNA is compacted several thousandfold by association with histones and non-histone proteins. The first step of compaction includes the formation of nucleosomes – the basic repeating units of chromatin. Further packaging occurs due to DNA binding to histone H1 and non-histone proteins involved in enhancer-promoter and insulator interactions. Under these conditions, the genome retains its functionality due to the dynamic and uneven DNA compaction along the chromatin fiber. Since the DNA compaction level affects the transcription activity of a certain genomic region, it is important to understand the interplay between the factors acting at different levels of the packaging process. Drosophila polytene chromosomes are an excellent model system for studying the molecular mechanisms that determine DNA compaction degree. The unevenness of DNA packaging along the chromatin fiber is easily observed along these chromosomes due to their large size and specific banding pattern. The purpose of this study was to figure out the role of two non-histone regulatory proteins, ADF1 and BEAF-32, in the DNA packaging process from nucleosome positioning to the establishment of the final chromosome structure. We studied the impact of mutations that affect ADF1 and BEAF-32 binding sites on the formation of 61C7/C8 interband – one of the decompacted regions of Drosophila polytene chromosomes. We show that such mutations led to the collapse of an interband, which was accompanied with increased nucleosome stability. We also find that ADF1 and BEAF-32 binding sites are essential for the rescue of lethality caused by the null allele of bantam microRNA gene located in the region 61C7/C8.

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Razin, Shmuel. "Adherence of Pathogenic Mycoplasmas to Host Cells." Bioscience Reports 19, no. 5 (October 1, 1999): 367–72. http://dx.doi.org/10.1023/a:1020204020545.

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The significant genome compaction in mycoplasmas was made possible by adoption of a parasitic lifestyle. During their evolution and adaptation to a parasitic mode of life the mycoplasmas have developed various genetic systems enabling their attachment to host tissues as well as a highly plastic set of variable surface proteins. The generation of a versatile surface coat through high-frequency phase and size variation provides the organism with a useful tool for immune system avoidance, allowing the mycoplasmas to escape antibody attack, explaining why these minute organisms are such successful parasites.

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Kapusta, Aurélie, Alexander Suh, and Cédric Feschotte. "Dynamics of genome size evolution in birds and mammals." Proceedings of the National Academy of Sciences 114, no. 8 (February 8, 2017): E1460—E1469. http://dx.doi.org/10.1073/pnas.1616702114.

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Genome size in mammals and birds shows remarkably little interspecific variation compared with other taxa. However, genome sequencing has revealed that many mammal and bird lineages have experienced differential rates of transposable element (TE) accumulation, which would be predicted to cause substantial variation in genome size between species. Thus, we hypothesize that there has been covariation between the amount of DNA gained by transposition and lost by deletion during mammal and avian evolution, resulting in genome size equilibrium. To test this model, we develop computational methods to quantify the amount of DNA gained by TE expansion and lost by deletion over the last 100 My in the lineages of 10 species of eutherian mammals and 24 species of birds. The results reveal extensive variation in the amount of DNA gained via lineage-specific transposition, but that DNA loss counteracted this expansion to various extents across lineages. Our analysis of the rate and size spectrum of deletion events implies that DNA removal in both mammals and birds has proceeded mostly through large segmental deletions (>10 kb). These findings support a unified “accordion” model of genome size evolution in eukaryotes whereby DNA loss counteracting TE expansion is a major determinant of genome size. Furthermore, we propose that extensive DNA loss, and not necessarily a dearth of TE activity, has been the primary force maintaining the greater genomic compaction of flying birds and bats relative to their flightless relatives.

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Watson, Andrew J., Gerald M. Kidder, and Gilbert A. Schultz. "How to make a blastocyst." Biochemistry and Cell Biology 70, no. 10-11 (October 1, 1992): 849–55. http://dx.doi.org/10.1139/o92-133.

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Several of the new reproductive technologies have been cultivated from our current understanding of the genetic programming and cellular processes that are involved in the major morphogenetic events of mammalian preimplantation development. Research directed at characterizing the patterns of gene expression during early development has shown that the embryo is initially under maternal control and later superseded by new transcriptional activity provided by the activation of the embryonic genome. Several embryonic transcripts encoding (i) growth factors, (ii) cell junctions, (iii) plasma membrane ion transporters, and (iv) cell adhesion molecules have been identified as contributing directly to the progression of the embryo through the preimplantation interval of development. In this brief review, we have outlined the patterns of expression and the integral roles that these gene families play in the morphogenetic events of compaction and cavitation. Research of this type has greatly facilitated our understanding of the control processes that underlie preimplantation development and represent but one area of this exciting and vigorous field of research.Key words: Na,K-ATPase, cavitation, compaction, preimplantation development, embryonic transcription.

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Jørgensen, Stine, Morten Eskildsen, Kasper Fugger, Lisbeth Hansen, Marie Sofie Yoo Larsen, Arne Nedergaard Kousholt, Randi G. Syljuåsen, et al. "SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation." Journal of Cell Biology 192, no. 1 (January 10, 2011): 43–54. http://dx.doi.org/10.1083/jcb.201009076.

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The eukaryotic cell cycle is regulated by multiple ubiquitin-mediated events, such as the timely destruction of cyclins and replication licensing factors. The histone H4 methyltransferase SET8 (Pr-Set7) is required for chromosome compaction in mitosis and for maintenance of genome integrity. In this study, we show that SET8 is targeted for degradation during S phase by the CRL4(CDT2) ubiquitin ligase in a proliferating cell nuclear antigen (PCNA)–dependent manner. SET8 degradation requires a conserved degron responsible for its interaction with PCNA and recruitment to chromatin where ubiquitylation occurs. Efficient degradation of SET8 at the onset of S phase is required for the regulation of chromatin compaction status and cell cycle progression. Moreover, the turnover of SET8 is accelerated after ultraviolet irradiation dependent on the CRL4(CDT2) ubiquitin ligase and PCNA. Removal of SET8 supports the modulation of chromatin structure after DNA damage. These results demonstrate a novel regulatory mechanism, linking for the first time the ubiquitin–proteasome system with rapid degradation of a histone methyltransferase to control cell proliferation.

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Cui, Jinteng, Zhanlu Zhang, Yang Shao, Kezhong Zhang, Pingsheng Leng, and Zhe Liang. "Genome-Wide Identification, Evolutionary, and Expression Analyses of Histone H3 Variants in Plants." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/341598.

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Histone variants alter the nucleosome structure and play important roles in chromosome segregation, transcription, DNA repair, and sperm compaction. Histone H3 is encoded by many genes in most eukaryotic species and is the histone that contains the largest variety of posttranslational modifications. Compared with the metazoan H3 variants, little is known about the complex evolutionary history of H3 variants proteins in plants. Here, we study the identification, evolutionary, and expression analyses of histone H3 variants from genomes in major branches in the plant tree of life. Firstly we identified all the histone three related (HTR) genes from the examined genomes, then we classified the four groups variants: centromeric H3, H3.1, H3.3 and H3-like, by phylogenetic analysis, intron information, and alignment. We further demonstrated that the H3 variants have evolved under strong purifying selection, indicating the conservation of HTR proteins. Expression analysis revealed that the HTR has a wide expression profile in maize and rice development and plays important roles in development.

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Miller, David, Martin Brinkworth, and David Iles. "Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics." REPRODUCTION 139, no. 2 (February 2010): 287–301. http://dx.doi.org/10.1530/rep-09-0281.

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Haploid male germ cells package their DNA into a volume that is typically 10% or less that of a somatic cell nucleus. To achieve this remarkable level of compaction, spermatozoa replace most of their histones with smaller, highly basic arginine and (in eutherians) cysteine rich protamines. One reason for such a high level of compaction is that it may help optimise nuclear shape and hence support the gametes' swimming ability for the long journey across the female reproductive tract to the oocyte. Super-compaction of the genome may confer additional protection from the effects of genotoxic factors. However, many species including the human retain a fraction of their chromatin in the more relaxed nucleosomal configuration that appears to run counter to the ergonomic, toroidal and repackaging of sperm DNA. Recent research suggests that the composition of this ‘residual’ nucleosomal compartment, a generally overlooked feature of the male gamete, is far more significant and important than previously thought. In this respect, the transport and incorporation of modified paternal histones by the spermatozoon to the zygote has been demonstrated and indicates another potential paternal effect in the epigenetic reprogramming of the zygote following fertilisation that is independent of imprinting status. In this review, the most recent research into mammalian spermatozoal chromatin composition is discussed alongside evidence for conserved, non-randomly located nucleosomal domains in spermatozoal nuclei, all supporting the hypothesis that the spermatozoon delivers a novel epigenetic signature to the egg that may be crucial for normal development. We also provide some thoughts on why this signature may be required in early embryogenesis.

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Qin, L., A. M. Erkelens, F. Ben Bdira, and R. T. Dame. "The architects of bacterial DNA bridges: a structurally and functionally conserved family of proteins." Open Biology 9, no. 12 (December 2019): 190223. http://dx.doi.org/10.1098/rsob.190223.

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Every organism across the tree of life compacts and organizes its genome with architectural chromatin proteins. While eukaryotes and archaea express histone proteins, the organization of bacterial chromosomes is dependent on nucleoid-associated proteins. In Escherichia coli and other proteobacteria, the histone-like nucleoid structuring protein (H-NS) acts as a global genome organizer and gene regulator. Functional analogues of H-NS have been found in other bacterial species: MvaT in Pseudomonas species, Lsr2 in actinomycetes and Rok in Bacillus species. These proteins complement hns − phenotypes and have similar DNA-binding properties, despite their lack of sequence homology. In this review, we focus on the structural and functional characteristics of these four architectural proteins. They are able to bridge DNA duplexes, which is key to genome compaction, gene regulation and their response to changing conditions in the environment. Structurally the domain organization and charge distribution of these proteins are conserved, which we suggest is at the basis of their conserved environment responsive behaviour. These observations could be used to find and validate new members of this protein family and to predict their response to environmental changes.

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Bao, Jianqiang, and Mark T. Bedford. "Epigenetic regulation of the histone-to-protamine transition during spermiogenesis." Reproduction 151, no. 5 (May 2016): R55—R70. http://dx.doi.org/10.1530/rep-15-0562.

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Abstract In mammals, male germ cells differentiate from haploid round spermatids to flagella-containing motile sperm in a process called spermiogenesis. This process is distinct from somatic cell differentiation in that the majority of the core histones are replaced sequentially, first by transition proteins and then by protamines, facilitating chromatin hyper-compaction. This histone-to-protamine transition process represents an excellent model for the investigation of how epigenetic regulators interact with each other to remodel chromatin architecture. Although early work in the field highlighted the critical roles of testis-specific transcription factors in controlling the haploid-specific developmental program, recent studies underscore the essential functions of epigenetic players involved in the dramatic genome remodeling that takes place during wholesale histone replacement. In this review, we discuss recent advances in our understanding of how epigenetic players, such as histone variants and histone writers/readers/erasers, rewire the haploid spermatid genome to facilitate histone substitution by protamines in mammals.

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Sekine, Eiki, Nora Schmidt, David Gaboriau, and Peter O’Hare. "Spatiotemporal dynamics of HSV genome nuclear entry and compaction state transitions using bioorthogonal chemistry and super-resolution microscopy." PLOS Pathogens 13, no. 11 (November 9, 2017): e1006721. http://dx.doi.org/10.1371/journal.ppat.1006721.

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Donaher, Natalie, Goro Tanifuji, Naoko T. Onodera, Stephanie A. Malfatti, Patrick S. G. Chain, Yoshiaki Hara, and John M. Archibald. "The Complete Plastid Genome Sequence of the Secondarily Nonphotosynthetic Alga Cryptomonas paramecium: Reduction, Compaction, and Accelerated Evolutionary Rate." Genome Biology and Evolution 1 (January 1, 2009): 439–48. http://dx.doi.org/10.1093/gbe/evp047.

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Widłak, Piotr. "DNA microarrays, a novel approach in studies of chromatin structure." Acta Biochimica Polonica 51, no. 1 (March 31, 2004): 1–8. http://dx.doi.org/10.18388/abp.2004_3592.

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The DNA microarray technology delivers an experimental tool that allows surveying expression of genetic information on a genome-wide scale at the level of single genes--for the new field termed functional genomics. Gene expression profiling--the primary application of DNA microarrays technology--generates monumental amounts of information concerning the functioning of genes, cells and organisms. However, the expression of genetic information is regulated by a number of factors that cannot be directly targeted by standard gene expression profiling. The genetic material of eukaryotic cells is packed into chromatin which provides the compaction and organization of DNA for replication, repair and recombination processes, and is the major epigenetic factor determining the expression of genetic information. Genomic DNA can be methylated and this modification modulates interactions with proteins which change the functional status of genes. Both chromatin structure and transcriptional activity are affected by the processes of replication, recombination and repair. Modified DNA microarray technology could be applied to genome-wide study of epigenetic factors and processes that modulate the expression of genetic information. Attempts to use DNA microarrays in studies of chromatin packing state, chromatin/DNA-binding protein distribution and DNA methylation pattern on a genome-wide scale are briefly reviewed in this paper.

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Jowhar, Ziad, Sigal Shachar, Prabhakar R. Gudla, Darawalee Wangsa, Erin Torres, Jill L. Russ, Gianluca Pegoraro, Thomas Ried, Armin Raznahan, and Tom Misteli. "Effects of human sex chromosome dosage on spatial chromosome organization." Molecular Biology of the Cell 29, no. 20 (October 2018): 2458–69. http://dx.doi.org/10.1091/mbc.e18-06-0359.

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Sex chromosome aneuploidies (SCAs) are common genetic syndromes characterized by the presence of an aberrant number of X and Y chromosomes due to meiotic defects. These conditions impact the structure and function of diverse tissues, but the proximal effects of SCAs on genome organization are unknown. Here, to determine the consequences of SCAs on global genome organization, we have analyzed multiple architectural features of chromosome organization in a comprehensive set of primary cells from SCA patients with various ratios of X and Y chromosomes by use of imaging-based high-throughput chromosome territory mapping (HiCTMap). We find that X chromosome supernumeracy does not affect the size, volume, or nuclear position of the Y chromosome or an autosomal chromosome. In contrast, the active X chromosome undergoes architectural changes as a function of increasing X copy number as measured by a decrease in size and an increase in circularity, which is indicative of chromatin compaction. In Y chromosome supernumeracy, Y chromosome size is reduced suggesting higher chromatin condensation. The radial positioning of chromosomes is unaffected in SCA karyotypes. Taken together, these observations document changes in genome architecture in response to alterations in sex chromosome numbers and point to trans-effects of dosage compensation on chromosome organization.

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Baergen, Allison K., Lucile M. Jeusset, Zelda Lichtensztejn, and Kirk J. McManus. "Diminished Condensin Gene Expression Drives Chromosome Instability That May Contribute to Colorectal Cancer Pathogenesis." Cancers 11, no. 8 (July 28, 2019): 1066. http://dx.doi.org/10.3390/cancers11081066.

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Chromosome instability (CIN), or constantly evolving chromosome complements, is a form of genome instability implicated in the development and progression of many cancer types, however, the molecular determinants of CIN remain poorly understood. Condensin is a protein complex involved in chromosome compaction, and recent studies in model organisms show that aberrant compaction adversely impacts mitotic fidelity. To systematically assess the clinical and fundamental impacts that reduced condensin gene expression have in cancer, we first assessed gene copy number alterations of all eight condensin genes. Using patient derived datasets, we show that shallow/deep deletions occur frequently in 12 common cancer types. Furthermore, we show that reduced expression of each gene is associated with worse overall survival in colorectal cancer patients. To determine the overall impact that reduced condensin gene expression has on CIN, a comprehensive siRNA-based screen was performed in two karyotypically stable cell lines. Following gene silencing, quantitative imaging microscopy identified increases in CIN-associated phenotypes, including changes in nuclear areas, micronucleus formation, and chromosome numbers. Although silencing corresponded with increases in CIN phenotypes, the most pronounced phenotypes were observed following SMC2 and SMC4 silencing. Collectively, our clinical and fundamental findings suggest reduced condensin expression and function may be a significant, yet, underappreciated driver of colorectal cancer.

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Harvey, A. J., K. L. Kind, and J. G. Thompson. "Effect of the oxidative phosphorylation uncoupler 2,4-dinitrophenol on hypoxia-inducible factor-regulated gene expression in bovine blastocysts." Reproduction, Fertility and Development 16, no. 7 (2004): 665. http://dx.doi.org/10.1071/rd04027.

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In cattle embryos, development to the blastocyst stage is improved in the presence of 10 μm 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, coincident with an increase in glycolytic activity following embryonic genome activation. The present study examined redox-sensitive gene expression and embryo development in response to the addition of DNP post-compaction. 2,4-Dinitrophenol increased the expression of hypoxia-inducible factor 1α and 2α (HIF1α, HIF2α) mRNA. Although HIF1α protein remained undetectable in bovine blastocysts, HIF2α protein was localised within the nucleus of trophectoderm and inner cell mass (ICM) cells of blastocysts cultured in the presence or absence of DNP, with a slight increase in staining evident within the ICM in blastocysts cultured in the presence of DNP. However, the expression of GLUT1 and VEGF mRNA, genes known to be regulated by HIFs, was unaffected by the addition of DNP to the culture. Although the development of Grade 1 and 2 blastocysts was unaltered by the addition of DNP post compaction in the present study, a significant increase in the proportion of ICM cells was observed. Results indicate that 10 μm DNP improves the quality of bovine embryos, coincident with increased HIF2α protein localisation within ICM cells and increased HIFα mRNA levels. Therefore, the results demonstrate redox-regulated expression of HIF2.

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Kuhn, Terra M., and Maya Capelson. "Nuclear Pore Proteins in Regulation of Chromatin State." Cells 8, no. 11 (November 9, 2019): 1414. http://dx.doi.org/10.3390/cells8111414.

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Nuclear pore complexes (NPCs) are canonically known to regulate nucleocytoplasmic transport. However, research efforts over the last decade have demonstrated that NPCs and their constituent nucleoporins (Nups) also interact with the genome and perform important roles in regulation of gene expression. It has become increasingly clear that many Nups execute these roles specifically through regulation of chromatin state, whether through interactions with histone modifiers and downstream changes in post-translational histone modifications, or through relationships with chromatin-remodeling proteins that can result in physical changes in nucleosome occupancy and chromatin compaction. This review focuses on these findings, highlighting the functional connection between NPCs/Nups and regulation of chromatin structure, and how this connection can manifest in regulation of transcription.

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Biggs, Ronald, Patrick Z. Liu, Andrew D. Stephens, and John F. Marko. "Effects of altering histone posttranslational modifications on mitotic chromosome structure and mechanics." Molecular Biology of the Cell 30, no. 7 (March 21, 2019): 820–27. http://dx.doi.org/10.1091/mbc.e18-09-0592.

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During cell division, chromatin is compacted into mitotic chromosomes to aid faithful segregation of the genome between two daughter cells. Posttranslational modifications (PTMs) of histones alter compaction of interphase chromatin, but it remains poorly understood how these modifications affect mitotic chromosome stiffness and structure. Using micropipette-based force measurements and epigenetic drugs, we probed the influence of canonical histone PTMs that dictate interphase euchromatin (acetylation) and heterochromatin (methylation) on mitotic chromosome stiffness. By measuring chromosome doubling force (the force required to double chromosome length), we find that histone methylation, but not acetylation, contributes to mitotic structure and stiffness. We discuss our findings in the context of chromatin gel modeling of the large-scale organization of mitotic chromosomes.

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Bukowska, D., B. Kempisty, H. Piotrowska, P. Sosinska, M. Wozna, S. Ciesiolka, and P. Antosik. " The structure and role of mammalian sperm RNA: a review." Veterinární Medicína 58, No. 2 (April 2, 2013): 57–64. http://dx.doi.org/10.17221/6696-vetmed.

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The main role of sperm is the delivery of the paternal genome into the oocyte during fertilisation. However, several lines of evidence have indicated that mammalian spermatozoa contribute more than just their DNA, namely, they also deliver a large range of RNA molecules. Microarray analysis has revealed a complex population of 3000 different kinds of messenger RNA that are delivered to oocytes by sperm and ejaculated spermatozoa are estimated to contain about 0.015 pg of total RNA. Some of the transcripts encode proteins crucial for early embryo development. Messenger RNAs from sperm also help to protect the paternal genes, which have an integral role soon after fertilisation. The molecular participation of the oocyte during fertilisation is well understood but the function of the sperm in this process remains unclear. During spermatogenesis the structure of the male haploid genome is permanently modified. Transition proteins (TNPs), protamines (PRMs) and histones (HILS-spermatid specific linker histone) play a unique role in spermatid chromatin compaction. In this review, the structure and role of sperm RNA as well as chromatin organisation during spermatogenesis are discussed.  

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Journal articles on the topic 'Genome Compaction'

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