Unknown

Dataset Information

0

Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver.


ABSTRACT: CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues. We propose that intra-TAD loops form by the same loop extrusion mechanism as the larger TAD loops, and that their shorter length enables finer regulatory control in restricting enhancer-promoter interactions, which enables selective, high-level expression of gene targets of super-enhancers and genes located within repressive nuclear compartments. These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity.

SUBMITTER: Matthews BJ 

PROVIDER: S-EPMC5986275 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver.

Matthews Bryan J BJ   Waxman David J DJ  

eLife 20180514


CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key  ...[more]

Similar Datasets

2018-05-11 | GSE102999 | GEO
| S-EPMC9811664 | biostudies-literature
| PRJNA399716 | ENA
| S-EPMC2448833 | biostudies-other
| S-EPMC7035113 | biostudies-literature
| S-EPMC6022626 | biostudies-literature
| S-EPMC10703910 | biostudies-literature
| S-EPMC5769866 | biostudies-literature
| S-EPMC5730888 | biostudies-literature
| S-EPMC8665748 | biostudies-literature