Cohesin
View article: Human cohesin compacts DNA by loop extrusion
Human cohesin compacts DNA by loop extrusion Open
Cohesin extrudes DNA loops DNA is folded into loops in eukaryotic cells by a process that depends on a ring-shaped adenosine triphosphatase complex called cohesin. Davidson et al. and Kim et al. now show that in the presence of the NIPBLMA…
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CTCF and cohesin regulate chromatin loop stability with distinct dynamics Open
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 gen…
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Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging Open
Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at …
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Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1 Open
It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structura…
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Compaction and segregation of sister chromatids via active loop extrusion Open
The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by…
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CTCF: making the right connections Open
The role of the zinc finger protein CTCF in organizing the genome within the nucleus is now well established. Widely separated sites on DNA, occupied by both CTCF and the cohesin complex, make physical contacts that create large loop domai…
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Emerging Evidence of Chromosome Folding by Loop Extrusion Open
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 facilitat…
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Recent evidence that TADs and chromatin loops are dynamic structures Open
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 chroma…
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Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders Open
TOP2B is positioned to solve topological problems at diverse cis-regulatory elements and its occupancy is a highly ordered and prevalent feature of CTCF/cohesin binding sites that flank TADs.
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CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention Open
The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa r…
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Cohesin and condensin extrude DNA loops in a cell cycle-dependent manner Open
Loop extrusion by structural maintenance of chromosomes (SMC) complexes has been proposed as a mechanism to organize chromatin in interphase and metaphase. However, the requirements for chromatin organization in these cell cycle phases are…
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Spindle asymmetry drives non-Mendelian chromosome segregation Open
How selfish genes get their way At the core of Mendelian genetics is the concept that gametes are equally likely to carry either of the two parental copies of a gene. Selfish genetic elements can cheat, however, by subverting Mendelian seg…
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Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin Open
Advanced FIB-SEM and 3D-SIM imaging uncover cohesin-independent chromatin arrangement into structural and functional modules.
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Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5 Open
Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, an…
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Transcription shapes 3D chromatin organization by interacting with loop extrusion Open
Cohesin folds mammalian interphase chromosomes by extruding the chromatin fiber into numerous loops. “Loop extrusion” can be impeded by chromatin-bound factors, such as CTCF, which generates characteristic and functional chromatin organiza…
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Molecular basis of CTCF binding polarity in genome folding Open
Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which …
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Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers Open
It is currently assumed that 3D chromosomal organization plays a central role in transcriptional control. However, depletion of cohesin and CTCF affects the steady-state levels of only a minority of transcripts. Here, we use high-resolutio…
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A Structure-Based Mechanism for DNA Entry into the Cohesin Ring Open
Despite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here we combine biochemical approaches and cryoelectron microscopy (cryo-EM) to visualiz…
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The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms Open
As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most …
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Bridging-induced phase separation induced by cohesin SMC protein complexes Open
Yeast cohesin complexes cluster onto long DNA into liquid droplets, which they accomplish by ATP-independent DNA bridging.
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A role for mitotic bookmarking of SOX2 in pluripotency and differentiation Open
Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M–G1) transition. However, mitotic bookmarking rem…
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Three-Dimensional Genomic Structure and Cohesin Occupancy Correlate with Transcriptional Activity during Spermatogenesis Open
Mammalian gametogenesis involves dramatic and tightly regulated chromatin remodeling, whose regulatory pathways remain largely unexplored. Here, we generate a comprehensive high-resolution structural and functional atlas of mouse spermatog…
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Determining cellular CTCF and cohesin abundances to constrain 3D genome models Open
Achieving a quantitative and predictive understanding of 3D genome architecture remains a major challenge, as it requires quantitative measurements of the key proteins involved. Here, we report the quantification of CTCF and cohesin, two c…
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CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion Open
In eukaryotes, genomic DNA is extruded into loops by cohesin 1 . By restraining this process, the DNA-binding protein CCCTC-binding factor (CTCF) generates topologically associating domains (TADs) 2,3 that have important roles in gene regu…
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RNA polymerases as moving barriers to condensin loop extrusion Open
To separate replicated sister chromatids during mitosis, eukaryotes and prokaryotes have structural maintenance of chromosome (SMC) condensin complexes that were recently shown to organize chromosomes by a process known as DNA loop extrusi…
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Hi-C analyses with GENOVA: a case study with cohesin variants Open
Conformation capture-approaches like Hi-C can elucidate chromosome structure at a genome-wide scale. Hi-C datasets are large and require specialised software. Here, we present GENOVA: a user-friendly software package to analyse and visuali…
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Establishment of DNA-DNA Interactions by the Cohesin Ring Open
The ring-shaped structural maintenance of chromosome (SMC) complexes are multi-subunit ATPases that topologically encircle DNA. SMC rings make vital contributions to numerous chromosomal functions, including mitotic chromosome condensation…
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Superresolution expansion microscopy reveals the three-dimensional organization of the <i>Drosophila</i> synaptonemal complex Open
Significance Because inaccurate chromosome segregation during meiosis is a leading cause of miscarriage in humans, we seek to understand how homologous chromosomes segregate properly. Meiotic chromosome segregation occurs with fidelity onl…
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The cohesin complex in mammalian meiosis Open
Cohesin is an evolutionary conserved multi‐protein complex that plays a pivotal role in chromosome dynamics. It plays a role both in sister chromatid cohesion and in establishing higher order chromosome architecture, in somatic and germ ce…
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Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy Open
Significance The ring-shaped cohesin traps chromosomes inside its ring and regulates chromosome segregation during mitosis and transcription during interphase. The sister chromatid cohesion 2 protein (Scc2) opens the cohesin ring and loads…