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Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.

Publication ,  Journal Article
Fufa, TD; Harris, ML; Watkins-Chow, DE; Levy, D; Gorkin, DU; Gildea, DE; Song, L; Safi, A; Crawford, GE; Sviderskaya, EV; Bennett, DC ...
Published in: Hum Mol Genet
October 1, 2015

SOX10 is required for melanocyte development and maintenance, and has been linked to melanoma initiation and progression. However, the molecular mechanisms by which SOX10 guides the appropriate gene expression programs necessary to promote the melanocyte lineage are not fully understood. Here we employ genetic and epigenomic analysis approaches to uncover novel genomic targets and previously unappreciated molecular roles of SOX10 in melanocytes. Through global analysis of SOX10-binding sites and epigenetic characteristics of chromatin states, we uncover an extensive catalog of SOX10 targets genome-wide. Our findings reveal that SOX10 predominantly engages 'open' chromatin regions and binds to distal regulatory elements, including novel and previously known melanocyte enhancers. Integrated chromatin occupancy and transcriptome analysis suggest a role for SOX10 in both transcriptional activation and repression to regulate functionally distinct classes of genes. We demonstrate that distinct epigenetic signatures and cis-regulatory sequence motifs predicted to bind putative co-regulatory transcription factors define SOX10-activated and SOX10-repressed target genes. Collectively, these findings uncover a central role of SOX10 as a global regulator of gene expression in the melanocyte lineage by targeting diverse regulatory pathways.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

October 1, 2015

Volume

24

Issue

19

Start / End Page

5433 / 5450

Location

England

Related Subject Headings

  • SOXE Transcription Factors
  • Oligonucleotide Array Sequence Analysis
  • Mice
  • Melanocytes
  • Genetics & Heredity
  • Gene Regulatory Networks
  • Gene Expression Profiling
  • Epigenomics
  • Chromatin
  • Cell Line
 

Citation

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Fufa, T. D., Harris, M. L., Watkins-Chow, D. E., Levy, D., Gorkin, D. U., Gildea, D. E., … Pavan, W. J. (2015). Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes. Hum Mol Genet, 24(19), 5433–5450. https://doi.org/10.1093/hmg/ddv267
Fufa, Temesgen D., Melissa L. Harris, Dawn E. Watkins-Chow, Denise Levy, David U. Gorkin, Derek E. Gildea, Lingyun Song, et al. “Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.Hum Mol Genet 24, no. 19 (October 1, 2015): 5433–50. https://doi.org/10.1093/hmg/ddv267.
Fufa TD, Harris ML, Watkins-Chow DE, Levy D, Gorkin DU, Gildea DE, et al. Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes. Hum Mol Genet. 2015 Oct 1;24(19):5433–50.
Fufa, Temesgen D., et al. “Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.Hum Mol Genet, vol. 24, no. 19, Oct. 2015, pp. 5433–50. Pubmed, doi:10.1093/hmg/ddv267.
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. Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes. Hum Mol Genet. 2015 Oct 1;24(19):5433–5450.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

October 1, 2015

Volume

24

Issue

19

Start / End Page

5433 / 5450

Location

England

Related Subject Headings

  • SOXE Transcription Factors
  • Oligonucleotide Array Sequence Analysis
  • Mice
  • Melanocytes
  • Genetics & Heredity
  • Gene Regulatory Networks
  • Gene Expression Profiling
  • Epigenomics
  • Chromatin
  • Cell Line