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 Delta Np63a 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 DNp63a; (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.

New p63 targets in keratinocytes identified by a genome-wide approach / M.A. Viganò, J. Lamartine, B. Testoni, D. Merico, D. Alotto, C. Castagnoli, A. Robert, E. Candi, G. Melino, X. Gidrol, R. Mantovani. - In: EMBO JOURNAL. - ISSN 0261-4189. - 25:21(2006 Nov 01), pp. 5105-5116. [10.1038/sj.emboj.7601375]

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

M.A. Viganò
Primo
;
B. Testoni;D. Merico;R. Mantovani
Ultimo
2006

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 Delta Np63a 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 DNp63a; (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.
ChIP on chip ; p63 ; skin ; targets
Settore BIO/18 - Genetica
1-nov-2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/62889
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