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Open Access Research article

Reciprocal regulation of p63 by C/EBP delta in human keratinocytes

Serena Borrelli1, Barbara Testoni1, Maurizio Callari1, Daniela Alotto2, Carlotta Castagnoli2, Rose-Anne Romano3, Satrajit Sinha3, Alessandra M Viganò1 and Roberto Mantovani1*

  • * Corresponding author: Roberto Mantovani mantor@unimi.it

  • † Equal contributors

Author Affiliations

1 Dipartimento di Scienze Biomolecolari e Biotecnologie. U. di Milano. Via Celoria 26, 20133 Milano, Italy

2 Dipartimento di Chirurgia Plastica-Banca della Cute, Ospedale CTO, Torino, Italy

3 Department of Biochemistry, SUNY, Buffalo, USA

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BMC Molecular Biology 2007, 8:85  doi:10.1186/1471-2199-8-85

Published: 28 September 2007

Abstract

Background

Genetic experiments have clarified that p63 is a key transcription factor governing the establishment and maintenance of multilayered epithelia. Key to our understanding of p63 strategy is the identification of target genes. We perfomed an RNAi screening in keratinocytes for p63, followed by profiling analysis.

Results

C/EBPδ, member of a family with known roles in differentiation pathways, emerged as a gene repressed by p63. We validated C/EBPδ as a primary target of ΔNp63α by RT-PCR and ChIP location analysis in HaCaT and primary cells. C/EBPδ is differentially expressed in stratification of human skin and it is up-regulated upon differentiation of HaCaT and primary keratinocytes. It is bound to and activates the ΔNp63 promoter. Overexpression of C/EBPδ leads to alteration in the normal profile of p63 isoforms, with the emergence of ΔNp63β and γ, and of the TA isoforms, with different kinetics. In addition, there are changes in the expression of most p63 targets. Inactivation of C/EBPδ leads to gene expression modifications, in part due to the concomitant repression of ΔNp63α. Finally, C/EBPδ is found on the p63 targets in vivo by ChIP analysis, indicating that coregulation is direct.

Conclusion

Our data highlight a coherent cross-talk between these two transcription factors in keratinocytes and a large sharing of common transcriptional targets.