Transport of DNA within cohesin involves clamping on top of engaged heads by Scc2 and entrapment within the ring by Scc3

eLife, Год журнала: 2020, Номер 9

Опубликована: Сен. 15, 2020

In addition to extruding DNA loops, cohesin entraps within its SMC-kleisin ring (S-K) individual DNAs during G1 and sister S-phase. All three activities require related hook-shaped proteins called Scc2 Scc3. Using thiol-specific crosslinking we provide rigorous proof of entrapment activity in vitro. alone promotes the E-S E-K compartments, between ATP-bound engaged heads SMC hinge associated kleisin, respectively. This does not ATP hydrolysis nor is it accompanied by S-K rings, which a slower process requiring Cryo-EM reveals that transported into E-S/E-K compartments are ‘clamped’ sub-compartment created Scc2’s association with whose coiled coils folded around their elbow. We suggest clamping may be recurrent feature complexes active loop extrusion this conformation precedes required for chromatid cohesion.

Язык: Английский

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Mechanisms of Chromosome Folding and Nuclear Organization: Their Interplay and Open Questions

Cold Spring Harbor Perspectives in Biology, Год журнала: 2021, Номер 14(7), С. a040147 - a040147

Опубликована: Сен. 13, 2021

Leonid Mirny1 and Job Dekker2 1Institute for Medical Engineering Science, Department of Physics, MIT, Cambridge, Massachusetts 02139, USA 2Howard Hughes Institute, Program in Systems Biology, Biochemistry Molecular Pharmacology, University School, Worcester, 01605, Correspondence: leonid{at}mit.edu; Job.Dekker{at}umassmed.edu

Язык: Английский

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CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism

Nucleus, Год журнала: 2020, Номер 11(1), С. 132 - 148

Опубликована: Янв. 1, 2020

Mammalian genome structure is closely linked to function. At the scale of kilobases megabases, CTCF and cohesin organize into chromatin loops. Mechanistically, proposed extrude loops bidirectionally until it encounters occupied DNA-binding sites. Curiously, form predominantly between binding sites in a convergent orientation. How interacts with blocks extrusion an orientation-specific manner has remained mechanistic mystery. Here, we review recent papers that have shed light on these processes suggest multi-step interaction cohesin. This may first involve pausing step, where halts extrusion, followed by stabilization step CTCF-cohesin complex, resulting loop. Finally, discuss our own studies internal RNA-Binding Region (RBRi) elucidate its role regulating clustering, target search mechanisms loop formation future challenges.

Язык: Английский

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CTCF-mediated chromatin looping provides a topological framework for the formation of phase-separated transcriptional condensates

Nucleic Acids Research, Год журнала: 2021, Номер 50(1), С. 207 - 226

Опубликована: Дек. 3, 2021

Abstract CTCF is crucial to the organization of mammalian genomes into loop structures. According recent studies, transcription apparatus compartmentalized and concentrated at super-enhancers form phase-separated condensates drive expression cell-identity genes. However, it remains unclear whether how transcriptional are coupled higher-order chromatin organization. Here, we show that essential for RNA polymerase II (Pol II)-mediated interactions, which occur as hyperconnected spatial clusters super-enhancers. We also demonstrate clustering, unlike Pol independent liquid-liquid phase-separation resistant perturbation transcription. Interestingly, II, BRD4, MED1 were found dissolve upon depletion, but reinstated restoration CTCF, suggesting a potent instructive function in formation condensates. Overall, provide evidence CTCF-mediated looping acts an architectural prerequisite assembly

Язык: Английский

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H3K27ac bookmarking promotes rapid post-mitotic activation of the pluripotent stem cell program without impacting 3D chromatin reorganization

Molecular Cell, Год журнала: 2021, Номер 81(8), С. 1732 - 1748.e8

Опубликована: Март 18, 2021

Язык: Английский

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