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Ctcf cohesin

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https://www.readbyqxmd.com/read/29757144/computational-prediction-of-ctcf-cohesin-based-intra-tad-loops-that-insulate-chromatin-contacts-and-gene-expression-in-mouse-liver
#1
Bryan J Matthews, David J Waxman
CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29728444/emerging-evidence-of-chromosome-folding-by-loop-extrusion
#2
Geoffrey Fudenberg, Nezar Abdennur, Maxim Imakaev, Anton Goloborodko, Leonid A Mirny
Chromosome organization poses a remarkable physical problem with many biological consequences: How can molecular interactions between proteins at the nanometer scale organize micron-long chromatinized DNA molecules, insulating or facilitating interactions between specific genomic elements? The mechanism of active loop extrusion holds great promise for explaining interphase and mitotic chromosome folding, yet remains difficult to assay directly. We discuss predictions from our polymer models of loop extrusion with barrier elements and review recent experimental studies that provide strong support for loop extrusion, focusing on perturbations to CTCF and cohesin assayed via Hi-C in interphase...
May 4, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#3
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
April 24, 2018: Cell
https://www.readbyqxmd.com/read/29702522/three-dimensional-genome-organization-in-normal-and-malignant-haematopoiesis
#4
Sergi Cuartero, Matthias Merkenschlager
PURPOSE OF REVIEW: The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer-promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29685368/principles-of-chromosome-architecture-revealed-by-hi-c
#5
REVIEW
Kyle P Eagen
Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops...
April 20, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29593713/variable-extent-of-lineage-specificity-and-developmental-stage-specificity-of-cohesin-and-ccctc-binding-factor-binding-within-the-immunoglobulin-and-t-cell-receptor-loci
#6
Salvatore Loguercio, E Mauricio Barajas-Mora, Han-Yu Shih, Michael S Krangel, Ann J Feeney
CCCTC-binding factor (CTCF) is largely responsible for the 3D architecture of the genome, in concert with the action of cohesin, through the creation of long-range chromatin loops. Cohesin is hypothesized to be the main driver of these long-range chromatin interactions by the process of loop extrusion. Here, we performed ChIP-seq for CTCF and cohesin in two stages each of T and B cell differentiation and examined the binding pattern in all six antigen receptor (AgR) loci in these lymphocyte progenitors and in mature T and B cells, ES cells, and fibroblasts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29590048/nascent-dna-methylome-mapping-reveals-inheritance-of-hemimethylation-at-ctcf-cohesin-sites
#7
Chenhuan Xu, Victor G Corces
The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation...
March 9, 2018: Science
https://www.readbyqxmd.com/read/29547555/dna-supercoiling-topoisomerases-and-cohesin-partners-in-regulating-chromatin-architecture
#8
Camilla Björkegren, Laura Baranello
Although our knowledge of chromatin organization has advanced significantly in recent years, much about the relationships between different features of genome architecture is still unknown. Folding of mammalian genomes into spatial domains is thought to depend on architectural proteins, other DNA-binding proteins, and different forms of RNA. In addition, emerging evidence points towards the possibility that the three-dimensional organisation of the genome is controlled by DNA topology. In this scenario, cohesin, CCCTC-binding factor (CTCF), transcription, DNA supercoiling, and topoisomerases are integrated to dictate different layers of genome organization, and the contribution of all four to gene control is an important direction of future studies...
March 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29507293/dissecting-super-enhancer-hierarchy-based-on-chromatin-interactions
#9
Jialiang Huang, Kailong Li, Wenqing Cai, Xin Liu, Yuannyu Zhang, Stuart H Orkin, Jian Xu, Guo-Cheng Yuan
Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants...
March 5, 2018: Nature Communications
https://www.readbyqxmd.com/read/29341686/nonequilibrium-chromosome-looping-via-molecular-slip-links
#10
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
We propose a model for the formation of chromatin loops based on the diffusive sliding of molecular slip links. These mimic the behavior of molecules like cohesin, which, along with the CTCF protein, stabilize loops which contribute to organizing the genome. By combining 3D Brownian dynamics simulations and 1D exactly solvable nonequilibrium models, we show that diffusive sliding is sufficient to account for the strong bias in favor of convergent CTCF-mediated chromosome loops observed experimentally. We also find that the diffusive motion of multiple slip links along chromatin is rectified by an intriguing ratchet effect that arises if slip links bind to the chromatin at a preferred "loading site...
September 29, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29335463/sub-kb-hi-c-in-d-melanogaster-reveals-conserved-characteristics-of-tads-between-insect-and-mammalian-cells
#11
Qi Wang, Qiu Sun, Daniel M Czajkowsky, Zhifeng Shao
Topologically associating domains (TADs) are fundamental elements of the eukaryotic genomic structure. However, recent studies suggest that the insulating complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those in Drosophila melanogaster, raising the possibility that border elements are not conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we show that the D. melanogaster genome is almost completely partitioned into >4000 TADs, nearly sevenfold more than previously identified...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316705/translocation-breakpoints-preferentially-occur-in-euchromatin-and-acrocentric-chromosomes
#12
Cheng-Yu Lin, Ankit Shukla, John P Grady, J Lynn Fink, Eloise Dray, Pascal H G Duijf
Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor...
January 8, 2018: Cancers
https://www.readbyqxmd.com/read/29300120/extrusion-without-a-motor-a-new-take-on-the-loop-extrusion-model-of-genome-organization
#13
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion...
January 1, 2018: Nucleus
https://www.readbyqxmd.com/read/29217591/topologically-associating-domains-and-chromatin-loops-depend-on-cohesin-and-are-regulated-by-ctcf-wapl-and-pds5-proteins
#14
Gordana Wutz, Csilla Várnai, Kota Nagasaka, David A Cisneros, Roman R Stocsits, Wen Tang, Stefan Schoenfelder, Gregor Jessberger, Matthias Muhar, M Julius Hossain, Nike Walther, Birgit Koch, Moritz Kueblbeck, Jan Ellenberg, Johannes Zuber, Peter Fraser, Jan-Michael Peters
Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops...
December 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29158440/cohesin-facilitates-zygotic-genome-activation-in-zebrafish
#15
Michael Meier, Jenny Grant, Amy Dowdle, Amarni Thomas, Jennifer Gerton, Philippe Collas, Justin M O'Sullivan, Julia A Horsfield
At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins cohesin and CCCTC-binding factor (CTCF) contribute to chromatin structure and gene regulation. We show here that normal cohesin function is important for ZGA in zebrafish. Depletion of the cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA, whereas complete abrogation is lethal...
January 3, 2018: Development
https://www.readbyqxmd.com/read/29140466/transcription-induced-supercoiling-as-the-driving-force-of-chromatin-loop-extrusion-during-formation-of-tads-in-interphase-chromosomes
#16
Dusan Racko, Fabrizio Benedetti, Julien Dorier, Andrzej Stasiak
Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders...
February 28, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133398/analysis-of-high-resolution-3d-intrachromosomal-interactions-aided-by-bayesian-network-modeling
#17
Xizhe Zhang, Sergio Branciamore, Grigoriy Gogoshin, Andrei S Rodin, Arthur D Riggs
Long-range intrachromosomal interactions play an important role in 3D chromosome structure and function, but our understanding of how various factors contribute to the strength of these interactions remains poor. In this study we used a recently developed analysis framework for Bayesian network (BN) modeling to analyze publicly available datasets for intrachromosomal interactions. We investigated how 106 variables affect the pairwise interactions of over 10 million 5-kb DNA segments in the B-lymphocyte cell line GB12878...
November 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29110030/the-emerging-roles-for-the-chromatin-structure-regulators-ctcf-and-cohesin-in-neurodevelopment-and-behavior
#18
REVIEW
Liron Davis, Itay Onn, Evan Elliott
Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior...
April 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29077530/recent-evidence-that-tads-and-chromatin-loops-are-dynamic-structures
#19
Anders S Hansen, Claudia Cattoglio, Xavier Darzacq, Robert Tjian
Mammalian genomes are folded into spatial domains, which regulate gene expression by modulating enhancer-promoter contacts. Here, we review recent studies on the structure and function of Topologically Associating Domains (TADs) and chromatin loops. We discuss how loop extrusion models can explain TAD formation and evidence that TADs are formed by the ring-shaped protein complex, cohesin, and that TAD boundaries are established by the DNA-binding protein, CTCF. We discuss our recent genomic, biochemical and single-molecule imaging studies on CTCF and cohesin, which suggest that TADs and chromatin loops are dynamic structures...
October 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28985562/cohesin-loss-eliminates-all-loop-domains
#20
Suhas S P Rao, Su-Chen Huang, Brian Glenn St Hilaire, Jesse M Engreitz, Elizabeth M Perez, Kyong-Rim Kieffer-Kwon, Adrian L Sanborn, Sarah E Johnstone, Gavin D Bascom, Ivan D Bochkov, Xingfan Huang, Muhammad S Shamim, Jaeweon Shin, Douglass Turner, Ziyi Ye, Arina D Omer, James T Robinson, Tamar Schlick, Bradley E Bernstein, Rafael Casellas, Eric S Lander, Erez Lieberman Aiden
The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected...
October 5, 2017: Cell
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