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Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution (ATAC-Seq)

ABSTRACT: Enhancer looping governs gene regulatory circuitry but is challenging to detect. Here we present Tri-4C, an ultrafine mapping method for distal chromatin contacts using triple restriction enzyme (RE) digestion. Tri-4C identifies enhancer loops that are undetectable by current single RE- based methods and reveals quantitative loop strengths in enhancer interaction networks underlying dynamic gene control. This multi-RE approach may be applied to general 3C-derived methods for accurate detection of enhancer loops.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119188 | GEO | 2020/08/28

REPOSITORIES: GEO

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Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution (Tri-4C)

Project description:Enhancer looping governs gene regulatory circuitry but is challenging to detect. Here we present Tri-4C, an ultrafine mapping method for distal chromatin contacts using triple restriction enzyme (RE) digestion. Tri-4C identifies enhancer loops that are undetectable by current single RE- based methods and reveals quantitative loop strengths in enhancer interaction networks underlying dynamic gene control. This multi-RE approach may be applied to general 3C-derived methods for accurate detection of enhancer loops.

2020-08-28 | GSE119187 | GEO

Ultrafine Mapping of Chromosome Conformation at hundred basepair resolution reveals regulatory genome architecture

Project description:The resolution limit of chromatin conformation capture methodologies (3Cs) has restrained their application in detection of fine-level chromatin structure mediated by cis-regulatory elements (CREs). Here we report two 3C-derived methods, Tri-4C and Tri-HiC, utilizing mult-restriction enzyme digestions capable of achieveing ultrafine genome digestion for targeted and global chromatin interaction mapping, respectively, at a one hundred basepair resolution. Tri-4C identified loops associated with CREs including those involving regulatory elements devoid of typical epigenomic marks, quantifatively revealing alterations in interaction networks underlying dynamic gene control. Tri-HiC successfully uncovers fine-gage enhancer:promoter (E:P) loops at genome-wide level, identifying > 20-fold more CRE loops than in situ HiC. In addition to refined loop detection, Tri-HiC also reveals interaction stripes and contact domain insulation from promoters and enhancers, revealing their loop extrusion behaviors resembling the topologically-associated domain (TAD) boundaries. Tri-4C and Tri-HiC provide robust approaches to achieve the high resolution interactome maps required for characterizing fine-gage regulatory chromatin interactions in analysis of development, homeostasis and disease.

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Project description:Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution (Tri-4C)

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Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution

Project description:Tri-4C: efficient and quantitative analysis of enhancer loops at hundred base pair resolution

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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.

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