title: Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation.
abstract: 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.
authors.affiliation: Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Barton
authors.forename: K N
authors.initials: KN
authors.lastname: Johnson
authors.forename: D M
authors.initials: DM
authors.lastname: Mays
authors.forename: K
authors.initials: K
authors.lastname: Boehnke
authors.forename: Y
authors.initials: Y
authors.lastname: Shyr
authors.forename: P
authors.initials: P
authors.lastname: Boukamp
authors.forename: J A
authors.initials: JA
authors.lastname: Pietenpol
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053582:Interleukin-1alpha; D034741:RNA, Small Interfering; C544912:TCF7L1 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins