Loss of Cohesin regulator PDS5A reveals repressive role of Polycomb loops
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA800030 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17721600_1.fastq.gz | Fastqsanger.gz | |||
| SRR17721600_2.fastq.gz | Fastqsanger.gz | |||
| SRR17721601_1.fastq.gz | Fastqsanger.gz | |||
| SRR17721601_2.fastq.gz | Fastqsanger.gz | |||
| SRR17721602_1.fastq.gz | Fastqsanger.gz |
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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
Project description:Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional gene silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. Additionally, 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 found that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of a subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not linked to loss of Polycomb chromatin domains. Instead, PDS5A removal causes aberrant cohesin activity leading to ectopic insulation sites, which disrupt the formation of ultra-long Polycomb loops. We show that these loops are important for robust silencing at a subset of PRC1/PRC2 target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.
| S-EPMC10710464 | biostudies-literature
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
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
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
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
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
Project description:Cohesin is crucial for proper chromosome segregation, but also regulates gene transcription and organism development by poorly understood mechanisms. We find that in Drosophila, cohesin functionally interacts with Polycomb group (PcG) silencing proteins at both silenced and active genes. Cohesin unexpectedly facilitates binding of Polycomb Repressive Complex 1 (PRC1) to many active genes. In contrast, cohesin and PRC1 binding are mutually antagonistic at silenced genes. PRC1 depletion decreases phosphorylated RNA polymerase and mRNA at many active genes, but increases them at silenced genes. Cohesin also facilitates long-range interactions between Polycomb Response Elements in the invected-engrailed gene complex where it represses transcription. These multiple distinct cohesin-PcG interactions reveal a previously unrecognized role for PRC1 in facilitating productive gene transcription, and provide new insights into how cohesin and PRC1 control development. ChIP-chip of cohesin, Polycomb group proteins, and RNA Polymerase II was performed in whole wing imaginal discs in developing wing imaginal disc, revealing that cohesin and Polycomb Repressive Complex 1 (PRC1) components co-bind with cohesin proteins at active genes. We then measured cohesin, Pc, and H3K27me3 separately in anterior and posterior wing imaginal discs and compared their binding at the invected-engrailed complex, which is silenced in the anterior disc, and expressed in its posterior. This confirmed that cohesin and PRC1 (Pc) co-bind at inv-en in its active state, and H3K27me3 and PRC1 (Pc) co-target inv-en in its silenced state. Comparison of binding between Pc-RJ and Pc-VP was performed, and revealed that Pc-VP is subject to epitope masking specifically at active genes. Finally, we measured cohesin and Pc binding in Drosophila ML-DmBG3-c2 cells, and found that they co-bind active genes in this cell line in as well as in wing imaginal discs. ChIP-chip of cohesin subunit Rad21 after PRC1 component Ph depletion, and ChIP-chip of PRC1 subunit Pc after Rad21 RNAi depletion, revealed that these two complexes affect one another's binding. Finally, ChIP-chip of Rpb3 (representing total Pol II) and Ser2P-Pol II (representing elongating Pol II) after PRC1 component Ph depletion revealed that PRC1 restrains entry of non-phosphorylated Pol II into gene bodies.
2013-04-25 | E-GEOD-42104 | biostudies-arrayexpress
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
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 | GSE209848 | GEO