Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Liesbeth Hoekman

LAB HEAD: Maarten Altelaar

PROVIDER: PXD032185 | Pride | 2022-03-14

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

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 acetylation cycle controls chromatin loop length through a PDS5A brake mechanism (synthetic viability screen)

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. Using a genome-wide haploid genetic screen 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 | GSE174627 | GEO

Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin dependent chromatin loops

Project description:Cohesin is a DNA translocase instrumental in the folding of the genome into chromatin loops, with functional consequences on DNA-related processes. Chromatin loop length and organization likely depend on cohesin processivity, translocation rate, and stability on DNA. Here we investigate and provide a comprehensive overview of the roles of various cohesin regulators in tuning chromatin loop expansion. We demonstrate that Scc2, which stimulates cohesin ATPase activity, is also essential for cohesin translocation, driving loop expansion in vivo. Smc3 acetylation during S-phase counteracts this activity through the stabilization of Pds5, which finely tunes the size and stability of loops in G2.

2022-02-23 | GSE186987 | GEO

Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL and PDS5 proteins

Project description:Mammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.

2017-12-07 | GSE102884 | GEO

Cohesin residency determines chromatin loop patterns

Project description:The organization of chromatin into higher-order structures is essential for chromosome segregation, the repair of DNA damage, and the regulation of gene expression. These structures are formed by the evolutionarily conserved SMC (structural maintenance of chromosomes) complexes. By analyzing synchronized populations of budding yeast with Micro-C, we observed that chromatin loops are formed genome-wide, and are dependent upon the SMC complex, cohesin. We correlated the loop signal with the position and intensity of cohesin binding to chromosomes in wild-type and cells depleted for the cohesin regulators Wpl1p and Pds5p. We generate a model to explain how the genomic distribution and frequency of loops are driven by cohesin residency on chromosomes. In this model a dynamic pool of cohesin with loop extrusion activity stops when encounters two regions occupied by stably bound cohesin, forming a loop. Different regions are occupied by cohesin in different cells, defining different patterns of chromatin loops.

2020-11-04 | GSE151553 | GEO

Cohesin residency determines chromatin loop patterns

2020-11-04 | GSE151416 | GEO

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [RNA-Seq]

Project description:Cohesin mediates sister chromatid cohesion and organizes the genome through the formation of chromatin loops. Two versions of the complex carrying either STAG1 or STAG2 show overlapping and specific functions and both are required to fulfill embryonic development. Cohesin-STAG1 displays longer residence time on chromatin that depends on CTCF and ESCO1 and establishes longer, long-lived chromatin loops together with CTCF. Cohesin-STAG2 shows a preferential interaction with WAPL and mediates shorter loops involved in tissue-specific transcription independently of CTCF. Here we show that the two variants respond in opposite ways to knock down of NIPBL, the putative cohesin loader that is also essential for loop extrusion. Cohesin-STAG1 levels increase on chromatin under this condition and the complex accumulates further at CTCF positions while cohesin-STAG2 is diminished genome-wide. Our data support a model in which NIPBL is not required for association of cohesin with chromatin but it is for loop extrusion, which in turn facilitates stabilization of cohesin-STAG2 at CTCF positions after being loaded elsewhere. In contrast, cohesin-STAG1 is preferentially loaded at CTCF sites independently of NIPBL. Nevertheless, loop formation by these chromatin-bound complexes is impaired and gene expression is severely affected, resembling alterations in Cornelia de Lange patients

2023-01-30 | GSE207110 | GEO

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [Hi-C]

2023-01-30 | GSE207115 | GEO

Response of cohesin STAG1 and STAG2 to reduction of NIPBL levels [ChIP-Seq]

2023-01-30 | GSE207113 | GEO