WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation.
Animals
Binding Sites
Cell Cycle Proteins
/ metabolism
Cell Differentiation
/ genetics
Cell Line
Chromatin
/ metabolism
Chromosomal Proteins, Non-Histone
/ metabolism
DNA-Binding Proteins
/ metabolism
Enhancer Elements, Genetic
/ genetics
Gene Expression Regulation
Mice
Models, Biological
Mouse Embryonic Stem Cells
/ cytology
Pluripotent Stem Cells
/ metabolism
Proteins
/ metabolism
Transcription Factors
/ metabolism
Transcription, Genetic
Cohesins
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
09
2019
accepted:
27
10
2020
pubmed:
16
12
2020
medline:
11
2
2021
entrez:
15
12
2020
Statut:
ppublish
Résumé
The cohesin complex has an essential role in maintaining genome organization. However, its role in gene regulation remains largely unresolved. Here we report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type-specific binding sites. Paradoxically, stabilization of cohesin binding, following WAPL ablation, results in depletion of cohesin from these cell-type-specific regions, loss of gene expression and differentiation. Chromosome conformation capture experiments show that cohesin turnover is important for maintaining promoter-enhancer loops. Binding of cohesin to cell-type-specific sites is dependent on the pioneer transcription factors OCT4 (POU5F1) and SOX2, but not NANOG. We show the importance of cohesin turnover in controlling transcription and propose that a cycle of cohesin loading and off-loading, instead of static cohesin binding, mediates promoter and enhancer interactions critical for gene regulation.
Identifiants
pubmed: 33318687
doi: 10.1038/s41588-020-00744-4
pii: 10.1038/s41588-020-00744-4
pmc: PMC7610352
mid: EMS118022
doi:
Substances chimiques
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
Proteins
0
Rad21 protein, mouse
0
Transcription Factors
0
WAPL protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100-109Subventions
Organisme : European Research Council
ID : 637587
Pays : International
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