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

Title
Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation
Authors
Lee K.E.Nam S.Cho E.-A.Seong I.Limb J.-K.Lee S.Kim J.
Ewha Authors
이상혁김재상
SCOPUS Author ID
이상혁scopus; 김재상scopus
Issue Date
2008
Journal Title
BMC Genomics
ISSN
1471-2164JCR Link
Citation
vol. 9
Indexed
SCIE; SCOPUS WOS scopus
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. © 2008 Lee et al; licensee BioMed Central Ltd.
DOI
10.1186/1471-2164-9-408
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자연과학대학 > 생명과학전공 > Journal papers
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