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Beyond MITF : Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma
Author(s) -
Seberg Hannah E.,
Van Otterloo Eric,
Cornell Robert A.
Publication year - 2017
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12611
Subject(s) - microphthalmia associated transcription factor , transcription factor , sox10 , biology , irf4 , neural crest , phenotype , microbiology and biotechnology , transcription (linguistics) , melanocyte , genetics , gene , melanoma , linguistics , philosophy
Summary MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of MITF activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, MITF does not act alone. Here, we review literature on the transcription factors that co‐regulate MITF ‐dependent genes. Ch IP ‐seq studies have indicated that the transcription factors SOX 10, YY 1, and TFAP 2A co‐occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF 1, RB 1, IRF 4, and PAX 3 acting in combination with MITF , while sequence motif analyses suggest that additional transcription factors colocalize with MITF at many melanocyte‐specific regulatory elements. However, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen‐patterned tissues during embryogenesis, we anticipate that the level of MITF activity is controlled not only by the concentration of activated MITF , but also by additional transcription factors that either quantitatively or qualitatively influence the expression of MITF ‐target genes.