Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation

J Investig Dermatol Symp Proc. 2001 Nov;6(1):99-104. doi: 10.1046/j.0022-202x.2001.00010.x.


Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditory-pigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5' to 3' direction, each of which encodes the unique N-terminus of a given isoform. The 5'-flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation*
  • Humans
  • Microphthalmia-Associated Transcription Factor
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction
  • Tietze's Syndrome / genetics
  • Transcription Factors*
  • Waardenburg Syndrome / genetics
  • Wnt Proteins
  • Zebrafish Proteins*


  • DNA-Binding Proteins
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins