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

被引:101
作者
Vigano, M. Alessandra
Lamartine, Jerome
Testoni, Barbara
Merico, Daniele
Alotto, Daniela
Castagnoli, Carlotta
Robert, Amelie
Candi, Eleonora
Melino, Gerry
Gidrol, Xavier
Mantovani, Roberto
机构
[1] Univ Milan, Dept Biomol Sci & Biotechnol, I-20133 Milan, Italy
[2] CEA, Serv Genom Fonct, Genopole Evry, France
[3] Osp CTO, Dipartimento Chirurg Plast, Turin, Italy
[4] Univ Rome, Dept Expt Med & Biochem Sci, IDI IRCCS, Rome, Italy
基金
英国医学研究理事会;
关键词
ChIP on chip; p63; skin; targets;
D O I
10.1038/sj.emboj.7601375
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:5105 / 5116
页数:12
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