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

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

PROVIDER: PRJNA488419 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7765290_1.fastq.gz	Fastqsanger.gz
	SRR7765290_2.fastq.gz	Fastqsanger.gz
	SRR7765300_1.fastq.gz	Fastqsanger.gz
	SRR7765300_2.fastq.gz	Fastqsanger.gz
	SRR7765310_1.fastq.gz	Fastqsanger.gz

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

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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.

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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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