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.

中文翻译：

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超越MITF：多种转录因子直接调节黑素细胞和黑色素瘤中的细胞表型。

MITF控制黑素细胞发育的多个步骤，包括神经c，生长，存活和终末分化的指标。另外，MITF活性的水平决定了黑色素瘤细胞采用的表型，无论是侵入性的，增生的还是分化的。但是，MITF并不单独行动。在这里，我们回顾有关共同调节MITF依赖基因的转录因子的文献。ChIP-seq研究表明，转录因子SOX10，YY1和TFAP2A共同占据了黑色素细胞中由MITF结合的调控元件的子集。单个基因座的分析也支持LEF1，RB1，IRF4和PAX3与MITF结合起作用的作用，而序列基序分析表明其他转录因子与MITF在许多黑素细胞特异性调节元件上共定位。然而，这些MITF合作者各自的确切生化功能及其对基因表达的贡献仍有待阐明。类似于胚胎发生过程中形态发生模式组织中的转录网络，我们预期MITF活性的水平不仅受激活的MITF浓度的控制，而且还受定量或定性影响MITF靶标表达的其他转录因子的控制基因。