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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains

ABSTRACT: Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains

PROVIDER: PRJNA421963 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6350680_1.fastq.gz	Fastqsanger.gz
	SRR6350680_2.fastq.gz	Fastqsanger.gz
	SRR6350690_1.fastq.gz	Fastqsanger.gz
	SRR6350690_2.fastq.gz	Fastqsanger.gz
	SRR6350700_1.fastq.gz	Fastqsanger.gz

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Capture-C]

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Hi-C]

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Tri-C]

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Hi-C]

Project description:The genome is organized into self-interacting chromatin domains containing genes and the cis-regulatory elements controlling their expression. How these domains form and how elements within them interact is unknown. We have developed Tri-C, a sensitive, high-resolution Chromosome Conformation Capture (3C) approach to identify concurrent chromatin interactions in single cells. Combining Tri-C with conventional 3C and polymer modeling, we show that, rather than folding into stable pre-formed loops, self-interacting domains form dynamic compartmentalized chromatin structures, delimited by CTCF/Cohesin boundaries. Within these tissue-specific domains, all regions of chromatin contact each other, but preferential structures are formed in which multiple enhancers and promoters interact simultaneously. Flanking CTCF/Cohesin-bound elements are excluded from these interactions and form distinct structures. These observations are best explained by a dynamic loop extrusion mechanism and subsequent stabilization of enhancer-promoter interactions, rather than the current view of long-range interactions occurring via the formation of discrete pre-formed chromatin loops.

2018-08-17 | GSE107939 | GEO

Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Tri-C]

Project description:The genome is organized into self-interacting chromatin domains containing genes and the cis-regulatory elements controlling their expression. How these domains form and how elements within them interact is not fully understood. We have developed Tri-C, a sensitive, high-resolution Chromosome Conformation Capture (3C) approach to identify concurrent chromatin interactions in single cells. Combining Tri-C with conventional 3C and polymer modeling, we show that, rather than folding into stable pre-formed loops, self-interacting domains form dynamic compartmentalized chromatin structures, delimited by CTCF/Cohesin boundaries. Within these tissue-specific domains, all regions of chromatin contact each other, but preferential structures are formed in which multiple enhancers and promoters interact simultaneously. Flanking CTCF/Cohesin-bound elements are excluded from these interactions and form distinct structures. These observations are best explained by a dynamic loop extrusion mechanism and subsequent stabilization of enhancer-promoter interactions, rather than the current view of long-range interactions occurring via the formation of discrete pre-formed chromatin loops.

2018-08-17 | GSE107755 | GEO

Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains [Capture-C]

Project description:The genome is organized into self-interacting chromatin domains containing genes and the cis-regulatory elements controlling their expression. How these domains form and how elements within them interact is not fully understood. We have developed Tri-C, a sensitive, high-resolution Chromosome Conformation Capture (3C) approach to identify concurrent chromatin interactions in single cells. Combining Tri-C with conventional 3C and polymer modeling, we show that, rather than folding into stable pre-formed loops, self-interacting domains form dynamic compartmentalized chromatin structures, delimited by CTCF/Cohesin boundaries. Within these tissue-specific domains, all regions of chromatin contact each other, but preferential structures are formed in which multiple enhancers and promoters interact simultaneously. Flanking CTCF/Cohesin-bound elements are excluded from these interactions and form distinct structures. These observations are best explained by a dynamic loop extrusion mechanism and subsequent stabilization of enhancer-promoter interactions, rather than the current view of long-range interactions occurring via the formation of discrete pre-formed chromatin loops.

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains.

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Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains

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

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Project description:The nucleus is highly compartmentalized through the formation of distinct classes of membraneless domains, yet the composition and function of many of these structures is not well understood. Using APEX2-mediated proximity labelling and RNA sequencing, we surveyed transcripts associated with nuclear speckles, several additional domains, and the lamina. Remarkably, speckles and lamina are associated with distinct classes of retained introns enriched in genes that function in RNA processing, translation, and the cell cycle. In contrast to the lamina-proximal introns, retained introns associated with speckles are relatively short, GC-rich, and enriched for functional sites of RNA binding proteins that are concentrated in these domains. They are also highly differentially regulated across diverse cellular contexts, including the cell cycle. Our study thus provides a resource of nuclear domain-associated transcripts and further reveals speckles and lamina as hubs of distinct populations of retained introns linked to gene regulation and cell cycle progression.

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [ChIP-seq]

Project description:Recent sequencing-based experiments mapping ensemble interaction frequency among regulatory elements in cancer cells support the existence of complex topological assemblies of enhancers and promoters known as promoter-enhancer hubs or cliques. Yet, the prevalence of promoter-enhancer hubs in individual cells, factors regulating their dynamics and assembly, as well as their role in transcriptional dysregulation in cancer remain unclear. Here, we systematically integrated functional genomics, transcription factor screening, and optical mapping of promoter-enhancer interactions to identify key promoter-enhancer hubs, examine heterogeneity of their assembly, determine their regulators, and elucidate their role in gene expression control in individual triple negative breast cancer (TNBC) cells. Optical mapping of individual SOX9 and MYC alleles revealed the existence of frequent multiway interactions among gene promoters and enhancers within promoter-enhancer hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 promoter-enhancer hubs, respectively. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies controlled by oncogenic transcription factors potentially in a cancer subtype-restricted manner to facilitate aberrant gene expression.

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