YY1 regulates melanocyte development and function by cooperating with MITF

Juying Li, Jun S. Song, Robert J.A. Bell, Thanh Nga T. Tran, Rizwan Haq, Huifei Liu, Kevin T. Love, Robert Langer, Daniel G. Anderson, Lionel Larue, David E. Fisher

Research output: Contribution to journalArticle

Abstract

Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)-a general mechanism which may confer tissue-specific gene expression in multiple lineages.

Original languageEnglish (US)
Article numbere1002688
JournalPLoS genetics
Volume8
Issue number5
DOIs
StatePublished - May 2012

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Li, J., Song, J. S., Bell, R. J. A., Tran, T. N. T., Haq, R., Liu, H., Love, K. T., Langer, R., Anderson, D. G., Larue, L., & Fisher, D. E. (2012). YY1 regulates melanocyte development and function by cooperating with MITF. PLoS genetics, 8(5), [e1002688]. https://doi.org/10.1371/journal.pgen.1002688