Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation

C. E. Barton, K. N. Johnson, D. M. Mays, K. Boehnke, Y. Shyr, P. Boukamp, J. A. Pietenpol

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55 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號e74
期刊Cell Death and Disease
1
發行號9
DOIs
出版狀態Published - 2010 9月

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

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