Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 May 2024
10 May 2024
Historique:
received:
12
11
2022
accepted:
23
04
2024
medline:
11
5
2024
pubmed:
11
5
2024
entrez:
10
5
2024
Statut:
epublish
Résumé
MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.
Identifiants
pubmed: 38729993
doi: 10.1038/s41467-024-48258-5
pii: 10.1038/s41467-024-48258-5
doi:
Substances chimiques
Proto-Oncogene Proteins c-myc
0
Myc protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3931Subventions
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PGC2018-096486-B-I00
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : CEX2020-001041-S
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : SC1-BHC-07-2019
Organisme : Comunidad de Madrid
ID : P2022/BMD-7245 CARDIOBOOST-CM
Informations de copyright
© 2024. The Author(s).
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