Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis.

Autor:	Kurinna S; Division of Cell Matrix Biology and Regenerative Medicine, FBMH, University of Manchester, M13 9PT, United Kingdom., Seltmann K; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland., Bachmann AL; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland., Schwendimann A; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland., Thiagarajan L; Division of Cell Matrix Biology and Regenerative Medicine, FBMH, University of Manchester, M13 9PT, United Kingdom., Hennig P; Department of Dermatology, University Hospital Zurich, 8006 Zurich, Switzerland., Beer HD; Department of Dermatology, University Hospital Zurich, 8006 Zurich, Switzerland., Mollo MR; CEINGE Biotecnologie Avanzate, Naples, Italy, University of Naples Federico II, 80131 Naples, Italy., Missero C; CEINGE Biotecnologie Avanzate, Naples, Italy, University of Naples Federico II, 80131 Naples, Italy., Werner S; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2021 Apr 19; Vol. 49 (7), pp. 3748-3763.
DOI:	10.1093/nar/gkab167
Abstrakt:	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. (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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