Beyond MITF: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma

• Published in: Pigment cell and melanoma research Vol. 30; no. 5; pp. 454 - 466
• Main Authors: Seberg, Hannah E., Van Otterloo, Eric, Cornell, Robert A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2017
• Subjects: Animals; AP-2 protein; Differentiation; Embryogenesis; Embryonic growth stage; Gene expression; Genes; Humans; Interferon regulatory factor 4; Literature reviews; Melanocytes; Melanocytes - metabolism; Melanocytes - pathology; Melanoma; Melanoma - metabolism; Melanoma - pathology; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - chemistry; Microphthalmia-Associated Transcription Factor - metabolism; MITF; Models, Biological; Neural crest; Pax3 protein; Phenotype; Regulatory sequences; SOX10; Sox10 protein; TFAP2A; Tissues; Transcription factors; Transcription Factors - metabolism; YY1; YY1 protein; TFAP2A; YY1; MITF; melanocytes; SOX10
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12611

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. ChIP‐seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co‐occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 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.