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Unraveling the cohesin-chromatin interface: identifying protein interactions that modulate chromosome structure and function [Micro-C]

ABSTRACT: Cohesin is a plieotropic regulator of genom structure and function with several known interactors that aid in regulation of genome organization. A comprehensive cohesin interactome has yet to be established, and we identify several chromatin regulating complexes that interact with the cohesin complex, including the SWI/SNF chromatin remodeling complex. SWI/SNF and cohesin co-localize to enhancers, promoters, and CTCF binding sites as deteremined by overlapping ChIP-seq data from mESCs for the cohesin subunit RAD21 and the SWI/SNF subunit BRG1, CTCF, H3K27ac, and H3K4me3. To assessthe functional implications of the cohesin-SWI/SNF interaction we treated mESCs with one of three small molecule drugs targeting the BRG1 subunit of SWI/SNF (ACBI1, PFI-3, BRM014) for either degradation of the complex or perturbation of SWI/SNF function, then performed ChIP-seq for the RAD21 subunit of cohesin. Differential RAD21 peaks in cells treated with a small molecule compared to DMSO control were assessed for overlap with DNA loops (Micro-C).

ORGANISM(S): Mus musculus

PROVIDER: GSE288456 | GEO | 2025/06/02

REPOSITORIES: GEO

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Unraveling the cohesin-chromatin interface: identifying protein interactions that modulate chromosome structure and function [ChIP-Seq]

Project description:Cohesin is a plieotropic regulator of genom structure and function with several known interactors that aid in regulation of genome organization. A comprehensive cohesin interactome has yet to be established, and we identify several chromatin regulating complexes that interact with the cohesin complex, including the SWI/SNF chromatin remodeling complex. SWI/SNF and cohesin co-localize to enhancers, promoters, and CTCF binding sites as deteremined by overlapping ChIP-seq data from mESCs for the cohesin subunit RAD21 and the SWI/SNF subunit BRG1, CTCF, H3K27ac, and H3K4me3. To assessthe functional implications of the cohesin-SWI/SNF interaction we treated mESCs with one of three small molecule drugs targeting the BRG1 subunit of SWI/SNF (ACBI1, PFI-3, BRM014) for either degradation of the complex or perturbation of SWI/SNF function, then performed ChIP-seq for the RAD21 subunit of cohesin. Differential RAD21 peaks in cells treated with a small molecule compared to DMSO control were assessed for overlap with DNA loops (Micro-C).

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Exploring the interaction between the SWI/SNF chromatin remodeling complex and the zinc finger factor CTCF

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Brd7, a novel PBAF-specific SWI/SNF subunit, is required for gene activation and repression in embryonic stem cells

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ARID1A deficiency weakens BRG1-RAD21 interaction that jeopardizes chromatin compactness and drives HCC metastasis [ChIP-seq]

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Project description:The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression, however aberrant remodeling and gene expression can result in cancer. The function and localization on chromatin of the SWI/SNF complex depends on the protein makeup of the complex. Here we report the protein-protein interactions of wild-type BRG1 or mutant BRG1 in which the HSA domain has been deleted (BRG1-HSA). We demonstrate the interaction of BRG1 with most SWI/SNF complex members and a failure of a number of these members to interact with BRG1-HSA. These results demonstrate that the HSA domain of BRG1 is a critical interaction platform for the correct formation of SWI/SNF remodeling complexes.

2023-02-15 | PXD029647 | Pride

Xist RNA antagonizes the chromatin remodeler, BRG1, from the inactive X chromosome

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2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress

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2013-12-02 | E-GEOD-52231 | biostudies-arrayexpress

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [ChIP-Seq]

Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs In order to understanding the lineage specific requirement of coactivaor, such as Brg1 and Brd4, in AML, we performed ChIP-seq with Brg1, Brd4 together with histone modification marks in murine MLL-AF9/NrasG12D AML cell line to search tissue specific cis regulation element that can be accounted for the leukemia specific dependence.

2013-12-02 | E-GEOD-52277 | biostudies-arrayexpress

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