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Dev Cell. 2012 Mar 13;22(3):669-77. doi: 10.1016/j.devcel.2011.12.001. Epub 2012 Feb 23.

ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.

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  • 1Department of Medicine/Cellular and Molecular Medicine, University of California-San Diego School of Medicine, La Jolla, CA 92093, USA.

Abstract

Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting that it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22364861
[PubMed - indexed for MEDLINE]
PMCID:
PMC3306457
Free PMC Article
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