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

Serena Borrelli, Barbara Testoni, Maurizio Callari, Daniela Alotto, Carlotta Castagnoli, Rose Anne Romano, Satrajit Sinha, Alessandra M. Viganò, Roberto Mantovani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number85
JournalBMC Molecular Biology
Volume8
DOIs
Publication statusPublished - Sep 28 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Fingerprint Dive into the research topics of 'Reciprocal regulation of p63 by C/EBP delta in human keratinocytes'. Together they form a unique fingerprint.

  • Cite this

    Borrelli, S., Testoni, B., Callari, M., Alotto, D., Castagnoli, C., Romano, R. A., Sinha, S., Viganò, A. M., & Mantovani, R. (2007). Reciprocal regulation of p63 by C/EBP delta in human keratinocytes. BMC Molecular Biology, 8, [85]. https://doi.org/10.1186/1471-2199-8-85