CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
23
07
2020
accepted:
02
04
2021
pubmed:
19
5
2021
medline:
31
8
2021
entrez:
18
5
2021
Statut:
ppublish
Résumé
Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer-promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.
Identifiants
pubmed: 34002095
doi: 10.1038/s41588-021-00863-6
pii: 10.1038/s41588-021-00863-6
pmc: PMC8853952
mid: NIHMS1755458
doi:
Substances chimiques
CCCTC-Binding Factor
0
CTCF protein, human
0
Chromatin
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
1064-1074Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK107977
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG011585
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA252020
Pays : United States
Organisme : NIMH NIH HHS
ID : U19 MH114830
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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