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Ctcf cohesin

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https://www.readbyqxmd.com/read/28542178/uncovering-direct-and-indirect-molecular-determinants-of-chromatin-loops-using-a-computational-integrative-approach
#1
Raphaël Mourad, Lang Li, Olivier Cuvier
Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs...
May 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28525739/genome-organization-cohesin-on-the-move
#2
Judita Richterova, Barbora Huraiova, Juraj Gregan
Folding of mammalian genomes into spatial domains is thought to depend on cohesin and CTCF proteins. Busslinger et al. (2017) reveal that transcription moves cohesin along DNA to CTCF-binding sites, providing insights into how cohesin and CTCF mediate chromosomal interactions by formation of chromatin loops.
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28475897/the-cohesin-release-factor-wapl-restricts-chromatin-loop-extension
#3
Judith H I Haarhuis, Robin H van der Weide, Vincent A Blomen, J Omar Yáñez-Cuna, Mario Amendola, Marjon S van Ruiten, Peter H L Krijger, Hans Teunissen, René H Medema, Bas van Steensel, Thijn R Brummelkamp, Elzo de Wit, Benjamin D Rowland
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs)...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28467304/ctcf-and-cohesin-regulate-chromatin-loop-stability-with-distinct-dynamics
#4
Anders S Hansen, Iryna Pustova, Claudia Cattoglio, Robert Tjian, Xavier Darzacq
Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1-2 min vs. ~22 min residence time)...
May 3, 2017: ELife
https://www.readbyqxmd.com/read/28428255/nucleosome-nucleosome-interactions-via-histone-tails-and-linker-dna-regulate-nuclear-rigidity
#5
Yuta Shimamoto, Sachiko Tamura, Hiroshi Masumoto, Kazuhiro Maeshima
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We addressed this in the present study by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#6
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#7
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28368372/ercc1-xpf-cooperates-with-ctcf-and-cohesin-to%C3%A2-facilitate-the-developmental-silencing-of-imprinted%C3%A2-genes
#8
Georgia Chatzinikolaou, Zivkos Apostolou, Tamara Aid-Pavlidis, Anna Ioannidou, Ismene Karakasilioti, Giorgio L Papadopoulos, Michalis Aivaliotis, Maria Tsekrekou, John Strouboulis, Theodore Kosteas, George A Garinis
Inborn defects in DNA repair are associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28262505/distinct-roles-of-brd2-and-brd4-in-potentiating-the-transcriptional-program-for-th17-cell-differentiation
#9
Ka Lung Cheung, Fan Zhang, Anbalagan Jaganathan, Rajal Sharma, Qiang Zhang, Tsuyoshi Konuma, Tong Shen, June-Yong Lee, Chunyan Ren, Chih-Hung Chen, Geming Lu, Matthew R Olson, Weijia Zhang, Mark H Kaplan, Dan R Littman, Martin J Walsh, Huabao Xiong, Lei Zeng, Ming-Ming Zhou
The BET proteins are major transcriptional regulators and have emerged as new drug targets, but their functional distinction has remained elusive. In this study, we report that the BET family members Brd2 and Brd4 exert distinct genomic functions at genes whose transcription they co-regulate during mouse T helper 17 (Th17) cell differentiation. Brd2 is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation. In this context, Brd2 binds the transcription factor Stat3 in an acetylation-sensitive manner and facilitates Stat3 recruitment to active enhancers occupied with transcription factors Irf4 and Batf...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28252665/chromatin-states-shape-insertion-profiles-of-the-piggybac-tol2-and-sleeping-beauty-transposons-and-murine-leukemia-virus
#10
Junko Yoshida, Keiko Akagi, Ryo Misawa, Chikara Kokubu, Junji Takeda, Kyoji Horie
DNA transposons and retroviruses are versatile tools in functional genomics and gene therapy. To facilitate their application, we conducted a genome-wide insertion site profiling of the piggyBac (PB), Tol2 and Sleeping Beauty (SB) transposons and the murine leukemia virus (MLV) in mouse embryonic stem cells (ESCs). PB and MLV preferred highly expressed genes, whereas Tol2 and SB preferred weakly expressed genes. However, correlations with DNase I hypersensitive sites were different for all vectors, indicating that chromatin accessibility is not the sole determinant...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178516/chromatin-states-in-mouse-sperm-correlate-with-embryonic-and-adult-regulatory-landscapes
#11
Yoon Hee Jung, Michael E G Sauria, Xiaowen Lyu, Manjinder S Cheema, Juan Ausio, James Taylor, Victor G Corces
The mammalian sperm genome is thought to lack substantial information for the regulation of future expression after fertilization. Here, we show that most promoters in mouse sperm are flanked by well-positioned nucleosomes marked by active histone modifications. Analysis of these modifications suggests that many enhancers and super-enhancers functional in embryonic and adult tissues are already specified in sperm. The sperm genome is bound by CTCF and cohesin at sites that are also present in round spermatids and embryonic stem cells (ESCs)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#12
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/27974201/functional-mutations-form-at-ctcf-cohesin-binding-sites-in-melanoma-due-to-uneven-nucleotide-excision-repair-across-the-motif
#13
Rebecca C Poulos, Julie A I Thoms, Yi Fang Guan, Ashwin Unnikrishnan, John E Pimanda, Jason W H Wong
CTCF binding sites are frequently mutated in cancer, but how these mutations accumulate and whether they broadly perturb CTCF binding are not well understood. Here, we report that skin cancers exhibit a highly specific asymmetric mutation pattern within CTCF motifs attributable to ultraviolet irradiation and differential nucleotide excision repair (NER). CTCF binding site mutations form independently of replication timing and are enriched at sites of CTCF/cohesin complex binding, suggesting a role for cohesin in stabilizing CTCF-DNA binding and impairing NER...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880868/origin-and-evolution-of-the-metazoan-non-coding-regulatory-genome
#14
REVIEW
Federico Gaiti, Andrew D Calcino, Miloš Tanurdžić, Bernard M Degnan
Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa...
November 20, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27863240/insulated-neighborhoods-structural-and-functional-units-of-mammalian-gene-control
#15
REVIEW
Denes Hnisz, Daniel S Day, Richard A Young
Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27851967/a-compendium-of-chromatin-contact-maps-reveals-spatially-active-regions-in-the-human-genome
#16
Anthony D Schmitt, Ming Hu, Inkyung Jung, Zheng Xu, Yunjiang Qiu, Catherine L Tan, Yun Li, Shin Lin, Yiing Lin, Cathy L Barr, Bing Ren
The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27799150/rapid-movement-and-transcriptional-re-localization-of-human-cohesin-on-dna
#17
Iain F Davidson, Daniela Goetz, Maciej P Zaczek, Maxim I Molodtsov, Pim J Huis In 't Veld, Florian Weissmann, Gabriele Litos, David A Cisneros, Maria Ocampo-Hafalla, Rene Ladurner, Frank Uhlmann, Alipasha Vaziri, Jan-Michael Peters
The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown...
December 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27742736/cohesin-mutations-in-cancer
#18
Magali De Koninck, Ana Losada
Cohesin is a large ring-shaped protein complex, conserved from yeast to human, which participates in most DNA transactions that take place in the nucleus. It mediates sister chromatid cohesion, which is essential for chromosome segregation and homologous recombination (HR)-mediated DNA repair. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement...
December 1, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27669308/making-sense-of-the-tangle-insights-into-chromatin-folding-and-gene-regulation
#19
REVIEW
Ill-Min Chung, Sarada Ketharnathan, Seung-Hyun Kim, Muthu Thiruvengadam, Mari Kavitha Rani, Govindasamy Rajakumar
Proximity ligation assays such as circularized chromosome conformation capture and high-throughput chromosome capture assays have shed light on the structural organization of the interphase genome. Functional topologically associating domains (TADs) that constitute the building blocks of genomic organization are disrupted and reconstructed during the cell cycle. Epigenetic memory, as well as the sequence of chromosomes, regulate TAD reconstitution. Sub-TAD domains that are invariant across cell types have been identified, and contacts between these domains, rather than looping, are speculated to drive chromatin folding...
September 23, 2016: Genes
https://www.readbyqxmd.com/read/27625394/maps-of-context-dependent-putative-regulatory-regions-and-genomic-signal-interactions
#20
Klev Diamanti, Husen M Umer, Marcin Kruczyk, Michał J Dąbrowski, Marco Cavalli, Claes Wadelius, Jan Komorowski
Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF-TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected ∼144k putative regulatory regions among the human cell-lines, with the majority of them being ∼300 bp...
September 12, 2016: Nucleic Acids Research
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