Mesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors.
Animals
Basic Helix-Loop-Helix Transcription Factors
/ metabolism
Cell Differentiation
/ genetics
Chromatin
/ genetics
Enhancer Elements, Genetic
/ genetics
Gene Expression Regulation, Developmental
Heart
Homeodomain Proteins
/ metabolism
Mammals
/ metabolism
Mesoderm
Mice
Transcription Factors
/ genetics
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
05
01
2021
accepted:
25
05
2022
pubmed:
12
7
2022
medline:
15
7
2022
entrez:
11
7
2022
Statut:
ppublish
Résumé
The mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 is a transcription factor that acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CPs remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the dynamic remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We identified Zic2 and Zic3 as essential cofactors that act with Mesp1 to regulate its transcription-factor activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
Identifiants
pubmed: 35817961
doi: 10.1038/s41556-022-00947-3
pii: 10.1038/s41556-022-00947-3
pmc: PMC7613098
mid: EMS145397
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Chromatin
0
Homeodomain Proteins
0
Mesp1 protein, mouse
0
Transcription Factors
0
Zic3 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1114-1128Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : European Research Council
ID : 885093
Pays : International
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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