Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
27
08
2019
accepted:
18
05
2020
pubmed:
24
6
2020
medline:
27
10
2020
entrez:
24
6
2020
Statut:
ppublish
Résumé
The human genome can be segmented into topologically associating domains (TADs), which have been proposed to spatially sequester genes and regulatory elements through chromatin looping. Interactions between TADs have also been suggested, presumably because of variable boundary positions across individual cells. However, the nature, extent and consequence of these dynamic boundaries remain unclear. Here, we combine high-resolution imaging with Oligopaint technology to quantify the interaction frequencies across both weak and strong boundaries. We find that chromatin intermingling across population-defined boundaries is widespread but that the extent of permissibility is locus-specific. Cohesin depletion, which abolishes domain formation at the population level, does not induce ectopic interactions but instead reduces interactions across all boundaries tested. In contrast, WAPL or CTCF depletion increases inter-domain contacts in a cohesin-dependent manner. Reduced chromatin intermingling due to cohesin loss affects the topology and transcriptional bursting frequencies of genes near boundaries. We propose that cohesin occasionally bypasses boundaries to promote incorporation of boundary-proximal genes into neighboring domains.
Identifiants
pubmed: 32572210
doi: 10.1038/s41588-020-0647-9
pii: 10.1038/s41588-020-0647-9
pmc: PMC7416539
mid: NIHMS1595869
doi:
Substances chimiques
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
840-848Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM128903
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008216
Pays : United States
Commentaires et corrections
Type : CommentIn
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