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

Kyung Eun Lee, Seungyoon Nam, Eun Ah Cho, Ikjoo Seong, Jin Kyung Limb, Sanghyuk Lee, Jaesang Kim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Article number408
JournalBMC Genomics
StatePublished - 11 Sep 2008

Bibliographical note

Funding Information:
This research was supported by a grant to JK (M103KV010007-06K2201-00710) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, by grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Education, Science & Technology (MEST) and the Korea Science and Engineering Foundation(KOSEF) through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University, by a grant to Ewha Research Center for Systems Biology (ERCSB) from Systems Biology Research Project of Gwangju Institute of Science & Technology (GIST), and by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2005-041-C00345) to JK. KL and EC were supported by fellowships from Brain Korea 21 Project.


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