Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
19 04 2021
19 04 2021
Historique:
accepted:
03
03
2021
revised:
27
02
2021
received:
01
10
2020
pubmed:
26
3
2021
medline:
13
5
2021
entrez:
25
3
2021
Statut:
ppublish
Résumé
Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63- a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia.
Identifiants
pubmed: 33764436
pii: 6188351
doi: 10.1093/nar/gkab167
pmc: PMC8053124
doi:
Substances chimiques
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
TP63 protein, human
0
Transcription Factors
0
Tumor Suppressor Proteins
0
CDK12 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3748-3763Subventions
Organisme : Medical Research Council
ID : MR/P009700/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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