SOX10, in combination with Sp1, regulates the <i>endothelin receptor type B</i> gene in human melanocyte lineage cells
抄録
<jats:p>Waardenburg syndrome (WS) is an auditory–pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS type 4 (WS4), a subtype of WS, is characterized by the presence of the aganglionic megacolon and is associated with mutations in the gene encoding either endothelin 3, endothelin receptor type B (EDNRB), or Sry‐box 10 (SOX10). Here, we provide evidence that SOX10 regulates the expression of <jats:italic>EDNRB</jats:italic> gene in human melanocyte‐lineage cells, as judged by RNA interference and chromatin immunoprecipitation analyses. Human melanocytes preferentially express the <jats:italic>EDNRB</jats:italic> transcripts derived from the conventional <jats:italic>EDNRB</jats:italic> promoter. SOX10 transactivates the <jats:italic>EDNRB</jats:italic> promoter through the <jats:italic>cis</jats:italic>‐acting elements, the two CA‐rich sequences and the GC box. Moreover, a transcription factor Sp1 enhances the degree of the SOX10‐mediated transactivation of the <jats:italic>EDNRB</jats:italic> promoter through these <jats:italic>cis</jats:italic>‐acting elements. Furthermore, we have shown that the <jats:italic>EDNRB</jats:italic> promoter is heavily methylated in HeLa human cervical cancer cells, lacking <jats:italic>EDNRB</jats:italic> expression, but not in melanocytes and HMV‐II melanoma cells. The expression of <jats:italic>EDNRB</jats:italic> became detectable in HeLa cells after treatment with a demethylating reagent, 5′‐aza‐2′‐deoxycytidine, which was further enhanced in the transformed cells over‐expressing SOX10. We therefore suggest that SOX10, alone or in combination with Sp1, regulates transcription of the <jats:italic>EDNRB</jats:italic> gene, thereby ensuring appropriate expression level of EDNRB in human melanocytes.</jats:p>
収録刊行物
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- The FEBS Journal
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The FEBS Journal 273 (8), 1805-1820, 2006-03-31
Wiley
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詳細情報 詳細情報について
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- CRID
- 1364233268345476992
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- NII論文ID
- 30014772296
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- ISSN
- 17424658
- 1742464X
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