TY - JOUR
T1 - New p63 targets in keratinocytes identified by a genome-wide approach
AU - Viganò, M. Alessandra
AU - Lamartine, Jérôme
AU - Testoni, Barbara
AU - Merico, Daniele
AU - Alotto, Daniela
AU - Castagnoli, Carlotta
AU - Robert, Amèlie
AU - Candi, Eleonora
AU - Melino, Gerry
AU - Gidrol, Xavier
AU - Mantovani, Roberto
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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.
AB - 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.
KW - ChIP on chip
KW - p63
KW - Skin
KW - Targets
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U2 - 10.1038/sj.emboj.7601375
DO - 10.1038/sj.emboj.7601375
M3 - Article
C2 - 17036050
AN - SCOPUS:33750480846
VL - 25
SP - 5105
EP - 5116
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 21
ER -