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Open Access Highly Accessed Research article

Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

Kyung Eun Lee1, Seungyoon Nam12, Eun-ah Cho1, Ikjoo Seong1, Jin-Kyung Limb1, Sanghyuk Lee1* and Jaesang Kim1*

Author Affiliations

1 Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul, 120-750, Korea

2 Interdisciplinary Program in Bioinformatics, Seoul National University, San 56-1, Shinlim-dong, Gwanak-gu, Seoul, 151-741, Korea

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BMC Genomics 2008, 9:408  doi:10.1186/1471-2164-9-408

Published: 11 September 2008

Abstract

Background

Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs.

Results

We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin) were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay.

Conclusion

In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.