microphthalmia, A critical factor in melanocyte development, defines a discrete transcription factor family

Timothy J. Hemesath, Eiríkur Steingrímsson, Gaël McGill, Michael J. Hansen, James Vaught, Colin A. Hodgkinson, Heinz Arnheiter, Neal G. Copeland, Nancy A. Jenkins, David E. Fisher

Research output: Contribution to journalArticle

507 Scopus citations

Abstract

The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice. It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH- ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TFEB, TFE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue-specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH- ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities.

Original languageEnglish (US)
Pages (from-to)2770-2780
Number of pages11
JournalGenes and Development
Volume8
Issue number22
DOIs
StatePublished - Nov 15 1994

Keywords

  • b-HLH-ZIP
  • dimerization
  • DNA binding
  • M box
  • microphthalmia

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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