Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states.
2C-like
EPC1
MERVL
RAP1
TIP60
ZSCAN4
telomere
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
received:
07
10
2021
accepted:
08
02
2022
pubmed:
26
2
2022
medline:
22
4
2022
entrez:
25
2
2022
Statut:
ppublish
Résumé
In mammals, the conserved telomere binding protein Rap1 serves a diverse set of nontelomeric functions, including activation of the NF-kB signaling pathway, maintenance of metabolic function in vivo, and transcriptional regulation. Here, we uncover the mechanism by which Rap1 modulates gene expression. Using a separation-of-function allele, we show that Rap1 transcriptional regulation is largely independent of TRF2-mediated binding to telomeres and does not involve direct binding to genomic loci. Instead, Rap1 interacts with the TIP60/p400 complex and modulates its histone acetyltransferase activity. Notably, we show that deletion of Rap1 in mouse embryonic stem cells increases the fraction of two-cell-like cells. Specifically, Rap1 enhances the repressive activity of Tip60/p400 across a subset of two-cell-stage genes, including
Identifiants
pubmed: 35210222
pii: gad.349039.121
doi: 10.1101/gad.349039.121
pmc: PMC8973845
doi:
Substances chimiques
Telomere-Binding Proteins
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
313-330Subventions
Organisme : NIDDK NIH HHS
ID : F30 DK118901
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102562
Pays : United States
Informations de copyright
© 2022 Barry et al.; Published by Cold Spring Harbor Laboratory Press.
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