New p63 targets in keratinocytes identified by a genome-wide approach

M. Alessandra Viganò, Jérôme Lamartine, Barbara Testoni, Daniele Merico, Daniela Alotto, Carlotta Castagnoli, Amèlie Robert, Eleonora Candi, Gerry Melino, Xavier Gidrol, Roberto Mantovani

Research output: Contribution to journalArticle

Abstract

p63 is a developmentally regulated transcription factor related to p53. It is involved in the development of ectodermal tissues, including limb, skin and in general, multilayered epithelia. The ΔNp63α isoform is thought to play a 'master' role in the asymmetric division of epithelial cells. It is also involved in the pathogenesis of several human diseases, phenotypically characterized by ectodermal dysplasia. Our understanding of transcriptional networks controlled by p63 is limited, owing to the low number of bona fide targets. To screen for new targets, we employed chromatin immunoprecipitation from keratinocytes (KCs) coupled to the microarray technology, using both CpG islands and promoter arrays. The former revealed 96 loci, the latter yielded 85 additional genes. We tested 40 of these targets in several functional assays, including: (i) in vivo binding by p63 in primary KCs; (ii) expression analysis in differentiating HaCaT cells and in cells overexpressing ΔNp63α; (iii) promoter transactivation and (iv) immunostaining in normal tissues, confirming their regulation by p63. We discovered several new specific targets whose functional categorization links p63 to cell growth and differentiation.

Original languageEnglish
Pages (from-to)5105-5116
Number of pages12
JournalEMBO Journal
Volume25
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

Keywords

  • ChIP on chip
  • p63
  • Skin
  • Targets

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Viganò, M. A., Lamartine, J., Testoni, B., Merico, D., Alotto, D., Castagnoli, C., Robert, A., Candi, E., Melino, G., Gidrol, X., & Mantovani, R. (2006). New p63 targets in keratinocytes identified by a genome-wide approach. EMBO Journal, 25(21), 5105-5116. https://doi.org/10.1038/sj.emboj.7601375