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  • The EMBO Journal (2006) 25, 5105 - 5116
  • doi:10.1038/sj.emboj.7601375

Published online: 12 October 2006

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

M Alessandra Viganò1, Jérôme Lamartine2, Barbara Testoni1, Daniele Merico1, Daniela Alotto3, Carlotta Castagnoli3, Amèlie Robert2, Eleonora Candi4, Gerry Melino4, Xavier Gidrol2 and Roberto Mantovani1

  1. Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita' di Milano, Milano, Italy
  2. Service de Génomique Fonctionnelle CEA, Genopole Evry, France
  3. Dipartimento di Chirurgia Plastica, Banca della Cute, Ospedale CTO, Torino, Italy
  4. IDI-IRCCS c/o Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy

Correspondence to:

Roberto Mantovani, Department of Biomolecular Sciences and Biotechnologies, University of Milan, Via Celoria, 26, Milan 20133, Italy. Tel.: +39 02 50315005; Fax: +39 02 50315044; E-mail: mantor@unimi.it

M Alessandra Viganò, Department of Biomolecular Sciences and Biotechnologies, University of Milan, Via Celoria, 26, Milan 20133, Italy. Tel.: +39 02 50315005; Fax: +39 02 50315044; E-mail: alessandra.vigano@guest.unimi.it

Received 16 May 2006; Accepted 28 August 2006

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 DeltaNp63alpha 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 DeltaNp63alpha; (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.

  • Keywords:

    • ChIP on chip,
    • p63,
    • skin,
    • targets