C/EBPd Gene Targets in Human Keratinocytes

Serena Borrelli, Daniele Fanoni, Diletta Dolfini, Daniela Alotto, Maria Ravo, Olì Maria Victoria Grober, Alessandro Weisz, Carlotta Castagnoli, Emilio Berti, M. Alessandra Vigano, Roberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

C/EBPs are a family of B-Zip transcription factors -TFs- involved in the regulation of differentiation in several tissues. The two most studied members -C/EBPα and C/EBPβ- play important roles in skin homeostasis and their ablation reveals cells with stem cells signatures. Much less is known about C/EBPδ which is highly expressed in the granular layer of interfollicular epidermis and is a direct target of p63, the master regular of multilayered epithelia. We identified C/EBPδ target genes in human primary keratinocytes by ChIP on chip and profiling of cells functionally inactivated with siRNA. Categorization suggests a role in differentiation and control of cell-cycle, particularly of G2/M genes. Among positively controlled targets are numerous genes involved in barrier function. Functional inactivation of C/EBPδ as well as overexpressions of two TF targets -MafB and SOX2- affect expression of markers of keratinocyte differentiation. We performed IHC on skin tumor tissue arrays: expression of C/EBPδ is lost in Basal Cell Carcinomas, but a majority of Squamous Cell Carcinomas showed elevated levels of the protein. Our data indicate that C/EBPδ plays a role in late stages of keratinocyte differentiation.

Original languageEnglish
Article numbere13789
JournalPLoS One
Volume5
Issue number11
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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