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Ctcf cohesin

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https://www.readbyqxmd.com/read/29341686/nonequilibrium-chromosome-looping-via-molecular-slip-links
#1
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
#2
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
#3
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
#4
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 4, 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
#5
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 7, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29158440/cohesin-facilitates-zygotic-genome-activation-in-zebrafish
#6
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 cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA whereas complete abrogation is lethal...
November 20, 2017: 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
#7
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...
November 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133398/analysis-of-high-resolution-3d-intrachromosomal-interactions-aided-by-bayesian-network-modeling
#8
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 13, 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
#9
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...
November 6, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29077530/recent-evidence-that-tads-and-chromatin-loops-are-dynamic-structures
#10
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
#11
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. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28938112/non-coding-transcription-instructs-chromatin-folding-and-compartmentalization-to-dictate-enhancer-promoter-communication-and-t-cell-fate
#12
Takeshi Isoda, Amanda J Moore, Zhaoren He, Vivek Chandra, Masatoshi Aida, Matthew Denholtz, Jan Piet van Hamburg, Kathleen M Fisch, Aaron N Chang, Shawn P Fahl, David L Wiest, Cornelis Murre
It is now established that Bcl11b specifies T cell fate. Here, we show that in developing T cells, the Bcl11b enhancer repositioned from the lamina to the nuclear interior. Our search for factors that relocalized the Bcl11b enhancer identified a non-coding RNA named ThymoD (thymocyte differentiation factor). ThymoD-deficient mice displayed a block at the onset of T cell development and developed lymphoid malignancies. We found that ThymoD transcription promoted demethylation at CTCF bound sites and activated cohesin-dependent looping to reposition the Bcl11b enhancer from the lamina to the nuclear interior and to juxtapose the Bcl11b enhancer and promoter into a single-loop domain...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28898712/inhibition-of-the-lytic-cycle-of-kaposi-s-sarcoma-associated-herpesvirus-by-cohesin-factors-following-de-novo-infection
#13
Zsolt Toth, Richard J Smindak, Bernadett Papp
Establishment of Kaposi's sarcoma-associated herpesvirus (KSHV) latency following infection is a multistep process, during which polycomb proteins are recruited onto the KSHV genome, which is crucial for the genome-wide repression of lytic genes during latency. Strikingly, only a subset of lytic genes are expressed transiently in the early phase of infection prior to the binding of polycomb proteins onto the KSHV genome, which raises the question what restricts lytic gene expression in the first hours of infection...
December 2017: Virology
https://www.readbyqxmd.com/read/28855971/the-effect-of-nipped-b-like-nipbl-haploinsufficiency-on-genome-wide-cohesin-binding-and-target-gene-expression-modeling-cornelia-de-lange-syndrome
#14
Daniel A Newkirk, Yen-Yun Chen, Richard Chien, Weihua Zeng, Jacob Biesinger, Ebony Flowers, Shimako Kawauchi, Rosaysela Santos, Anne L Calof, Arthur D Lander, Xiaohui Xie, Kyoko Yokomori
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder frequently associated with heterozygous loss-of-function mutations of Nipped-B-like (NIPBL), the human homolog of Drosophila Nipped-B. NIPBL loads cohesin onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis but is also increasingly recognized as a regulator of gene expression. In CdLS patient cells and animal models, expression changes of multiple genes with little or no sister chromatid cohesion defect suggests that disruption of gene regulation underlies this disorder...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28737770/tissue-specific-ctcf-cohesin-mediated-chromatin-architecture-delimits-enhancer-interactions-and-function-in-vivo
#15
Lars L P Hanssen, Mira T Kassouf, A Marieke Oudelaar, Daniel Biggs, Chris Preece, Damien J Downes, Matthew Gosden, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Jim R Hughes, Benjamin Davies, Douglas R Higgs
The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF-cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment...
August 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28735753/genome-organization-drives-chromosome-fragility
#16
Andres Canela, Yaakov Maman, Seolkyoung Jung, Nancy Wong, Elsa Callen, Amanda Day, Kyong-Rim Kieffer-Kwon, Aleksandra Pekowska, Hongliang Zhang, Suhas S P Rao, Su-Chen Huang, Peter J Mckinnon, Peter D Aplan, Yves Pommier, Erez Lieberman Aiden, Rafael Casellas, André Nussenzweig
In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28715449/a-unique-enhancer-boundary-complex-on-the-mouse-ribosomal-rna-genes-persists-after-loss-of-rrn3-or-ubf-and-the-inactivation-of-rna-polymerase-i-transcription
#17
Chelsea Herdman, Jean-Clement Mars, Victor Y Stefanovsky, Michel G Tremblay, Marianne Sabourin-Felix, Helen Lindsay, Mark D Robinson, Tom Moss
Transcription of the several hundred of mouse and human Ribosomal RNA (rRNA) genes accounts for the majority of RNA synthesis in the cell nucleus and is the determinant of cytoplasmic ribosome abundance, a key factor in regulating gene expression. The rRNA genes, referred to globally as the rDNA, are clustered as direct repeats at the Nucleolar Organiser Regions, NORs, of several chromosomes, and in many cells the active repeats are transcribed at near saturation levels. The rDNA is also a hotspot of recombination and chromosome breakage, and hence understanding its control has broad importance...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#18
REVIEW
Teruyoshi Hirayama, Takeshi Yagi
Individual neurons are basic functional units in the complex system of the brain. One aspect of neuronal individuality is generated by stochastic and combinatorial expression of diverse clustered protocadherins (Pcdhs), encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters, that are critical for several aspects of neural circuit formation. Each clustered Pcdh gene has its own promoter containing conserved sequences and is transcribed by a promoter choice mechanism involving interaction between the promoter and enhancers...
June 4, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28542178/uncovering-direct-and-indirect-molecular-determinants-of-chromatin-loops-using-a-computational-integrative-approach
#19
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 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28525739/genome-organization-cohesin-on-the-move
#20
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
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