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Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion [4C-seq]

ABSTRACT: Structural loops are known to collapse in the absence of cohesin, whereas regulatory loops largely persist with only minor transcriptional changes, leaving unresolved questions about cohesin’s role in establishing regulatory interactions during cell state transitions. To investigate this, we degraded RAD21, a core cohesin subunit, in mouse embryonic stem cells (ESCs) transitioning from mitosis to G1 under self-renewal or differentiation conditions. We performed high-resolution in situ 4C-seq around the promoters of cohesin-sensitive genes (Klf4, Tbx3, Myc, and Fosl2) in ESCs and EpiLCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE288298 | GEO | 2026/02/16

REPOSITORIES: GEO

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Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion [RNA-seq]

Project description:Structural loops are known to collapse in the absence of cohesin, whereas regulatory loops largely persist with only minor transcriptional changes, leaving unresolved questions about cohesin’s role in establishing regulatory interactions during cell state transitions. To investigate this, we degraded RAD21, a core cohesin subunit, in mouse embryonic stem cells (ESCs) transitioning from mitosis to G1 under self-renewal or differentiation conditions. We performed RNA-seq to profile gene expression in ESCs and EpiLCs.

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Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion [Micro-C]

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Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion [ChIP-seq]

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The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism

Project description:Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the 3D genome. ESCO1 restricts the length of chromatin loops and architectural stripes, while HDAC8 promotes the extension of such loops and stripes. This role in controlling loop length turns out to be distinct from the canonical role of cohesin acetylation that protects against WAPL-mediated DNA release. We reveal that acetylation rather controls cohesin’s interaction with PDS5A to restrict chromatin loop length. Our data supports a model in which this PDS5A-bound state acts as a brake that enables the pausing and restart of loop enlargement. The cohesin acetylation cycle hereby provides punctuation in the process of genome folding.

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Cohesin supercoils DNA during loop extrusion

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Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [Hi-C]

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2023-10-25 | GSE235771 | GEO

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [ChIP-seq]

2023-10-25 | GSE235770 | GEO

The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism (Hi-C)

Project description:Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids from S-phase until mitosis. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the 3D genome. ESCO1 restricts the length of chromatin loops and architectural stripes, while HDAC8 rather promotes the extension of such loops and stripes. This role in controlling loop length turns out to be distinct from the canonical role of cohesin acetylation that protects against WAPL-mediated DNA release. We reveal that acetylation rather controls cohesin’s interaction with PDS5A to restrict chromatin loop length. Our data supports a model in which this PDS5A-bound state acts as a brake that enables the pausing and restart of loop enlargement. The cohesin acetylation cycle hereby provides punctuation in the process of genome folding.

2022-03-14 | GSE150564 | GEO

The cohesin release factor WAPL restricts chromatin loop extension [ESS]

Project description:The spatial organization of chromosomes influences many nuclear processes including gene expression. The ring-shaped cohesin complex shapes the 3D genome by looping together convergent CTCF sites along chromosomes. We show here with high-resolution Hi-C analysis that chromatin loop size can be increased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL alsoincreased, and that cohesin’s DNA release factor WAPL restricts the degree of this extension. WAPL also prevents looping between incorrectly oriented CTCF sites. Through haploid genetics we find that WAPL deficiency bypasses the need for cohesin’s DNA loader SCC4 and we reveal that SCC4 promotes the extension of chromatin loops. We provide functional evidence in support of the model that chromatin loops are processively enlarged by the extrusion of DNA from cohesin rings. We conclude that the balanced activity of SCC4 and WAPL enables cohesin to correctly structure chromosomes to ensure proper transcriptional control.

2017-05-03 | GSE95521 | GEO

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