Cohesin chromatin loop formation by an extrinsic motor

Guérin, Thomas M.; Barrington, Christopher; Pobegalov, Georgii; Molodtsov, Maxim I.; Uhlmann, Frank

doi:10.1101/2023.11.30.569410

Cited by 4 publications

(2 citation statements)

References 84 publications

(135 reference statements)

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“…A very recent report revealed that purified yeast cohesin with Scc2-Scc4 exhibits DNA loop extrusion activity almost equivalent to that of human cohesin in vitro (Guérin et al, 2023). Our current study demonstrated that yeast cohesin is actually capable of forming large DNA loops of several hundred kb in vivo , comparable to those in human nuclei if Scc2-cohesin interaction is free from inhibitory regulation by Wpl1 and Eco1.…”

Section: Discussionmentioning

confidence: 99%

Controlling mechanism of the Scc2-cohesin interaction to restrict peri-centromeric DNA loop expansion and facilitate mitotic chromosome segregation

Nguyen,

Sakata,

Shirahige

et al. 2024

Preprint

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Cohesin exhibits DNA loop extrusion activity when bound to an ATPase activator Scc2 (NIPBL in humans), thereby organizing higher-order chromosome folding. In budding yeast, the majority of the chromosome-bound cohesins lack association with Scc2. It remains unknown how the interaction between Scc2 and cohesin is regulated on the chromosome and what physiological consequences malfunction in this regulatory mechanism causes. Here, we show that simultaneous deletion of Wpl1 and Eco1, two of the known cohesin regulators, resulted in Scc2 co-localization with cohesin around the centromeres of metaphase chromosomes. In these cells, the pericentromeric DNA loops were enlarged to connect the centromere to the cohesin/Scc2 co-bound sites at distances of up to a few hundred kb, indicating highly active loop extrusion by the Scc2-associated cohesin. Furthermore, we demonstrated that deltawpl1 deltaeco1 cells exhibited a delay in the progression of mitotic chromosome segregation, a phenotype dependent on the presence of Scc2 in metaphase. These findings suggest that Wpl1 and Eco1 cooperatively regulate Scc2-cohesin interaction on chromosomes, restrict the size of the pericentromeric DNA loops, and facilitate mitotic chromosome segregation.

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Section: Discussionmentioning

confidence: 99%

Controlling mechanism of the Scc2-cohesin interaction to restrict peri-centromeric DNA loop expansion and facilitate mitotic chromosome segregation

Nguyen,

Sakata,

Shirahige

et al. 2024

Preprint

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show abstract

“…18,19 On the other hand, cohesin mutants unable to exclude DNA have been observed to form chromatin loops in vivo . 20 Thus, the involvement of the loop extrusion activity in the formation of cohesin-mediated structures is still under debate. Cohesin is thought to regulate gene expression by modulating the contact frequency between promoters and enhancers through TADs and promoter-enhancer loops.…”

Section: Introductionmentioning

confidence: 99%

Cohesin regulates promoter-proximal pausing of RNA Polymerase II by limiting recruitment of super elongation complex

Tei,

Sakata,

Yoshimura

et al. 2024

Preprint

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Cohesin is a ring-shaped complex, responsible for establishing sister chromatid cohesion and forming topologically associating domains (TADs) and chromatin loops. Loss-of-function mutations in cohesin subunits and its regulatory factors can cause Cornelia de Lange syndrome (CdLS). Because dysregulated gene expression was observed in CdLS, it has long been thought that cohesin plays a regulatory role in transcription. Here, we investigated the effect of acute cohesin depletion on transcription and observed that a small number of genes exhibited differential expression. Analysis of RNA polymerase II (Pol II) distribution revealed that the depletion reduced Pol II promoter binding and pausing simultaneously at the majority of genes. This implies that at most genes, the two decreases counterbalance each other, resulting in unchanged gene expression. Additionally, we find that cohesin loss increased promoter binding of super elongation complex (SEC), which mediates the release of Pol II from paused state. Moreover, the reduction in pausing caused by cohesin depletion was no longer observed when SEC was inhibited. These observations suggest that cohesin regulates Pol II pausing by restricting SEC recruitment to promoters. Together, our study demonstrates the involvement of cohesin in transcriptional regulation, particularly in Pol II pause and release.

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Motorized chain models of the ideal chromosome

Cao,

Wolynes

2024

Proc. Natl. Acad. Sci. U.S.A.

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An array of motor proteins consumes chemical energy in setting up the architectures of chromosomes. Here, we explore how the structure of ideal polymer chains is influenced by two classes of motors. The first class which we call “swimming motors” acts to propel the chromatin fiber through three-dimensional space. They represent a caricature of motors such as RNA polymerases. Previously, they have often been described by adding a persistent flow onto Brownian diffusion of the chain. The second class of motors, which we call “grappling motors” caricatures the loop extrusion processes in which segments of chromatin fibers some distance apart are brought together. We analyze these models using a self-consistent variational phonon approximation to a many-body Master equation incorporating motor activities. We show that whether the swimming motors lead to contraction or expansion depends on the susceptibility of the motors, that is, how their activity depends on the forces they must exert. Grappling motors in contrast to swimming motors lead to long-ranged correlations that resemble those first suggested for fractal globules and that are consistent with the effective interactions inferred by energy landscape analyses of Hi-C data on the interphase chromosome.

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Cohesin chromatin loop formation by an extrinsic motor

Cited by 4 publications

References 84 publications

Controlling mechanism of the Scc2-cohesin interaction to restrict peri-centromeric DNA loop expansion and facilitate mitotic chromosome segregation

Controlling mechanism of the Scc2-cohesin interaction to restrict peri-centromeric DNA loop expansion and facilitate mitotic chromosome segregation

Cohesin regulates promoter-proximal pausing of RNA Polymerase II by limiting recruitment of super elongation complex

Motorized chain models of the ideal chromosome

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