Paul A. Khavari, MD, PhD

Publication Details

  • ZNF750 Is a p63 Target Gene that Induces KLF4 to Drive Terminal Epidermal Differentiation DEVELOPMENTAL CELL Sen, G. L., Boxer, L. D., Webster, D. E., Bussat, R. T., Qu, K., Zarnegar, B. J., Johnston, D., Siprashvili, Z., Khavari, P. A. 2012; 22 (3): 669-677

    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 linksĀ a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process.

    View details for DOI 10.1016/j.devcel.2011.12.001

    View details for Web of Science ID 000301701600020

    View details for PubMedID 22364861

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