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Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors

ABSTRACT: Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors

PROVIDER: PRJNA804917 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17870713_1.fastq.gz	Fastqsanger.gz
	SRR17870713_2.fastq.gz	Fastqsanger.gz
	SRR17870714_1.fastq.gz	Fastqsanger.gz
	SRR17870714_2.fastq.gz	Fastqsanger.gz
	SRR17870715_1.fastq.gz	Fastqsanger.gz

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Project description:Cohesin plays vital roles in chromatin folding and gene expression regulation, cooperating with such factors as cohesin loaders, unloaders, and the insulation factor CTCF. Although models of regulation have been proposed (e.g., loop extrusion), how cohesin and related factors collectively or individually regulate the hierarchical chromatin structure and gene expression remains unclear. We have depleted cohesin and related factors and then conducted a comprehensive evaluation of the resulting 3D genome, transcriptome and epigenome data. We observed substantial variation in depletion effects among factors at topologically associating domain (TAD) boundaries and on interTAD interactions, which were related to epigenomic status.

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Cohesin-mediated chromatin folding dynamics and transcriptional interactions

Project description:We apply ChIA-Drop, a single-molecule ligation-free mapping technique, to visualize loop formation over time. Our results demonstrated a cohesin-centric framework that coordinates with CTCF and RNAPII, respectively. At the loading (NIPBL binding) site, cohesin is highly correlated with transcriptional activities and translocates bi-directionally toward CTCF motif sites, where CTCF likely provides the anchoring point for cohesin to actively reel the chromatin template according to the motif forward orientation. Furthermore, cohesin specifically co-localizes with RNAPII and together mediates multiplex chromatin interactions that involve promoters, enhancers and super-enhancers. Intriguingly, single-molecule mapping data revealed that individual constituents of super-enhancers interact with target genes singularly and in cascade through intermediate regulatory elements, suggesting a probability-based mechanism for transcription regulation.

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Multiomic analysis of Cohesin reveals that ZBTB transcription factors contribute to chromatin interactions

Project description:One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the Cohesin in chromatin and identified transcription factors, RNA-binding proteins, and chromatin regulators associated with Cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to Cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with Cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in Cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of Cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with Cohesin that warrant further investigation.

2023-06-05 | PXD035893 | Pride