Genomic Analysis Reveals Distinct Mechanisms and Functional Classes of SOX10-Regulated Genes in Melanocytes [gene expression]

We performed ChIP-Seq analysis of SOX10, histone H3 lysine 27 acetylation (H3K27ac) and H3K27 trimethylation (H3K27me3) in melanocytes to profile the genomic binding sites of SOX10 and the chromatin landscape. In parallel, we generated Sox10 haploinsufficient cell lines using gene knockout approaches and conducted microarray gene expression analysis to identify functional gene targets of SOX10 transcriptional regulation in melanocytes. We demonstrate that SOX10 predominantly engages open chromatin, binds to melanocyte enhancer elements and plays a central role in transcriptional activation and repression of functionally distinct classes of genes. Furthermore, we identified cis-regulatory sequence motifs of putative co-regulatory transcription factors that define SOX10-activated and SOX10-repressed target genes. Our results uncover novel mechanisms and roles of SOX10 in global transcriptional regulation of diverse regulatory pathways in the melanocyte lineage.

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Fufa TD, Harris ML, Watkins-Chow DE, Levy D, Gorkin DU, Gildea DE, Song L, Safi A, Crawford GE, Sviderskaya EV, Bennett DC, Mccallion AS, Loftus SK, Pavan WJ