Genomics

Dataset Information

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


ABSTRACT: 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. Overall design: Capture-C combines 3C library preparation with oligonucleotide capture for the desired viewpoint restriction fragments. Experiments were performed in biological triplicates of primary erythroid and ES cells.

INSTRUMENT(S): Illumina MiSeq (Mus musculus)

SUBMITTER: A Marieke Oudelaar  

PROVIDER: GSE107753 | GEO | 2018-08-17

REPOSITORIES: GEO

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Publications


The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new chromosome conformation capture (3C) approach, to characterize concurrent chromatin interactions at individual alleles. Analysis by Tri-C identifies heterogeneous patterns of single-allele interactions  ...[more]

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