A chromatin immunoprecipitation screen in mouse keratinocytes reveals Runx1 as a direct transcriptional target of ΔNp63

Kori Ortt, Eli Raveh, Uri Gat, Satrajit Sinha*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Development of the skin epidermis and appendages such as hair follicles involves coordinated processes of keratinocyte proliferation and differentiation. The transcription factor p63 plays a critical role in these steps as evident by a complete lack of these structures in p63 null mice. The p63 gene encodes for two proteins TAp63 and ΔNp63, the latter being the more prevalent and dominant isoform expressed in keratinocytes. Although numerous p63 target genes have been identified, these studies have been limited to transformed human keratinocyte cell lines. Here, we have employed a genomic screening approach of chromatin immunoprecipitation (ChIP) coupled with an enrichment strategy to identify ΔNp63 response elements in primary mouse keratinocytes. Analysis of p63-ChlP-derived DNA segments has revealed more than 100 potential target genes including novel as well as mouse counterparts of established human p63 targets. Among these is Runx1, a transcription factor important for hair follicle development. We demonstrate that ΔNp63 binds to a p63-response element located within a well-conserved enhancer of the Runx1 gene. Furthermore, siRNAmediated reduction of ΔN63 in mouse keratinocytes reduces Runx1 expression. Consistent with this, endogenous Runx1 levels are lower in the skin of p63+/- animals as compared to wild type animals. Lastly, we demonstrate that ΔNp63 and Runx1 are co-expressed in specific compartments of the hair follicle in a dynamic fashion. Taken together our data demonstrate that p63 directly regulates Runx1 gene expression through a novel enhancer element and suggests a role for these two transcription factors in dictating skin keratinocyte and appendage development.

Original languageAmerican English
Pages (from-to)1204-1219
Number of pages16
JournalJournal of Cellular Biochemistry
Volume104
Issue number4
DOIs
StatePublished - 1 Jul 2008

Keywords

  • Chromatin immunoprecipitation
  • Hair follicle
  • Keratinocyte
  • Runx1
  • Transcription
  • p63

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