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

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

PROVIDER: PRJNA632826 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14577446_1.fastq.gz	Fastqsanger.gz
	SRR14577446_2.fastq.gz	Fastqsanger.gz
	SRR14577447_1.fastq.gz	Fastqsanger.gz
	SRR14577447_2.fastq.gz	Fastqsanger.gz
	SRR14577448_1.fastq.gz	Fastqsanger.gz

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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.

2022-03-14 | PXD032185 | Pride

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

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

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

| PRJNA730820 | ENA

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

Project description:The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism (synthetic viability screen)

| PRJNA730827 | ENA

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-14 | GSE174628 | GEO

PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome [ChIP-seq]

Project description:Purpose: Cohesin is an important structural regulator of the genome. Whether cohesin HEAT repeat accessory proteins PDS5A and PDS5B differentially contribute to cohesin function remains unclear. The purpose of this study is to interrogate how PDS5A and PDS5B affect cohesin localization and gene expression in mouse embronic stem cells (mESCs) Method: Genome wide binding patterns of PDS5A, PDS5B, and cohesin in wildtype cells as well as in PDS5 CRISPR/Cas9 genome edited knockout cells were assessed via chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq). The redundancy of the PDS5 subunits was addressed by using siRNA against PDS5B in a PDS5A-knockout background.

2022-08-21 | GSE199354 | GEO

PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome [RNA-seq]

Project description:Purpose: Cohesin is an important structural regulator of the genome. Whether cohesin HEAT repeat accessory proteins PDS5A and PDS5B differentially contribute to cohesin function remains unclear. The purpose of this study is to interrogate how PDS5A and PDS5B affect cohesin localization and gene expression in mouse embronic stem cells (mESCs) Method: The role of PDS5A and PDS5B in gene regulation was assessed by performing RNA-seq in wildtype and CRISPR-Cas9 genome edited PDS5 knockout mouse embryonic stem cells (mESCs). The redundancy of the PDS5s was addressed by using siRNA against PDS5B in a PDS5A-knockout background. Whether PDS5 and STAG proteins have selective roles in gene expression was addressed by using siRNA against STAG1 and STAG2 in a PDS5A-KO background

2022-08-21 | GSE199255 | GEO

Loss of Cohesin regulator PDS5A reveals repressive role of Polycomb loops

Project description:Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. In addition, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we discovered that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not associated with loss of repressive Polycomb chromatin modifications. Instead, loss of PDS5A leads to aberrant cohesin activity, ectopic insulation sites and specific reduction of ultra-long Polycomb loops. We infer that these loops are important for robust silencing at a subset of Polycomb target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.

2023-11-10 | GSE194268 | GEO

Regulation of cohesin-mediated chromosome structure by PDS5 in mammals [ChIP-seq]

Project description:Cohesin regulates sister chromatids cohesion but also contributes to chromosome folding by promoting the formation of chromatin loops, a process proposed to be mediated by loop extrusion. PDS5 plays a crucial role in regulating the cohesin dynamic on chromatin, mainly through WAPL-mediated release activity and the opponent ESCO1/2-sororin dependent pathway. However, the exact function of PDS5 on cohesin-mediated chromatin looping remains ambiguous. Two versions of PDS5 exist in vertebrates, PDS5A and PDS5B. Here, we construct cells for rapid PDS5A or PDS5B degradation in PLC/PRF/5 cell line with the FKBP12F36V-dTAG degron system to perform loss of function studies. Combining Hi-C, ChIP-seq for cohesin regulators, and RNA-seq data, we describe the redundant and discrete roles of PDS5A and PDS5B in three-dimensional genome organization and gene expression.

2022-10-08 | GSE209845 | GEO

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