TY - JOUR
T1 - Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation
AU - Barton, C. E.
AU - Johnson, K. N.
AU - Mays, D. M.
AU - Boehnke, K.
AU - Shyr, Y.
AU - Boukamp, P.
AU - Pietenpol, J. A.
N1 - Funding Information:
Acknowledgements. This work was supported by NIH Grants CA70856 and CA105436 (JAP), ES00267 and CA68485 (core services), and NIH Training Grant T32CA078136-08 (CEB). We thank Dr Christopher Barbieri for generating the shp63DBD retrovirus and Dr Leif Ellisen for providing the siRNA adenoviruses. The Krt2 antibody was kindly provided by Dr Lutz Langbein (DKFZ). We would like to thank members of the Pietenpol laboratory for critical reading of the manuscript and helpful discussions.
PY - 2010/9
Y1 - 2010/9
N2 - The transcription factor p63 is required for proper epidermal barrier formation and maintenance. Herein, we used chromatin immunoprecipitation coupled with DNA sequencing to identify novel p63 target genes involved in normal human epidermal keratinocyte (NHEKs) growth and differentiation. We identified over 2000 genomic sites bound by p63, of which 82 were also transcriptionally regulated by p63 in NHEKs. Through the discovery of interleukin-1-α as a p63 target gene, we identified that p63 is a regulator of epithelial-mesenchymal crosstalk. Further, three-dimensional organotypic co-cultures revealed TCF7L1, another novel p63 target gene, as a regulator of epidermal proliferation and differentiation, providing a mechanism by which p63 maintains the proliferative potential of basal epidermal cells. The discovery of new target genes links p63 to diverse signaling pathways required for epidermal development, including regulation of paracrine signaling to proliferative potential. Further mechanistic insight into p63 regulation of epidermal cell growth and differentiation is provided by the identification of a number of novel p63 target genes in this study.
AB - The transcription factor p63 is required for proper epidermal barrier formation and maintenance. Herein, we used chromatin immunoprecipitation coupled with DNA sequencing to identify novel p63 target genes involved in normal human epidermal keratinocyte (NHEKs) growth and differentiation. We identified over 2000 genomic sites bound by p63, of which 82 were also transcriptionally regulated by p63 in NHEKs. Through the discovery of interleukin-1-α as a p63 target gene, we identified that p63 is a regulator of epithelial-mesenchymal crosstalk. Further, three-dimensional organotypic co-cultures revealed TCF7L1, another novel p63 target gene, as a regulator of epidermal proliferation and differentiation, providing a mechanism by which p63 maintains the proliferative potential of basal epidermal cells. The discovery of new target genes links p63 to diverse signaling pathways required for epidermal development, including regulation of paracrine signaling to proliferative potential. Further mechanistic insight into p63 regulation of epidermal cell growth and differentiation is provided by the identification of a number of novel p63 target genes in this study.
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U2 - 10.1038/cddis.2010.49
DO - 10.1038/cddis.2010.49
M3 - Article
C2 - 21151771
AN - SCOPUS:79958279335
SN - 2041-4889
VL - 1
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 9
M1 - e74
ER -