TY - JOUR
T1 - Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis
AU - Kurinna, Svitlana
AU - Seltmann, Kristin
AU - Bachmann, Andreas L.
AU - Schwendimann, Andreas
AU - Thiagarajan, Lalitha
AU - Hennig, Paulina
AU - Beer, Hans-Dietmar
AU - Mollo, Maria Rosaria
AU - Missero, Caterina
AU - Werner, Sabine
PY - 2021/4/19
Y1 - 2021/4/19
N2 - 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.
AB - 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.
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_starter&SrcAuth=WosAPI&KeyUT=WOS:000649006000018&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1093/nar/gkab167
DO - 10.1093/nar/gkab167
M3 - Article
C2 - 33764436
SN - 0305-1048
VL - 49
SP - 3748
EP - 3763
JO - Nucleic Acids Res
JF - Nucleic Acids Res
IS - 7
ER -
