Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
03
09
2022
accepted:
15
05
2023
medline:
13
7
2023
pubmed:
16
6
2023
entrez:
15
6
2023
Statut:
ppublish
Résumé
During development, Hox genes are temporally activated according to their relative positions on their clusters, contributing to the proper identities of structures along the rostrocaudal axis. To understand the mechanism underlying this Hox timer, we used mouse embryonic stem cell-derived stembryos. Following Wnt signaling, the process involves transcriptional initiation at the anterior part of the cluster and a concomitant loading of cohesin complexes enriched on the transcribed DNA segments, that is, with an asymmetric distribution favoring the anterior part of the cluster. Chromatin extrusion then occurs with successively more posterior CTCF sites acting as transient insulators, thus generating a progressive time delay in the activation of more posterior-located genes due to long-range contacts with a flanking topologically associating domain. Mutant stembryos support this model and reveal that the presence of evolutionary conserved and regularly spaced intergenic CTCF sites controls the precision and the pace of this temporal mechanism.
Identifiants
pubmed: 37322110
doi: 10.1038/s41588-023-01426-7
pii: 10.1038/s41588-023-01426-7
pmc: PMC10335938
doi:
Substances chimiques
CCCTC-Binding Factor
0
Chromatin
0
DNA
9007-49-2
Ctcf protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1164-1175Informations de copyright
© 2023. The Author(s).
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