SOX10, in combination with Sp1, regulates the endothelin receptor type B gene in human melanocyte lineage cells

Satoru Yokoyama, Kazuhisa Takeda, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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 EDNRB gene in human melanocyte-lineage cells, as judged by RNA interference and chromatin immunoprecipitation analyses. Human melanocytes preferentially express the EDNRB transcripts derived from the conventional EDNRB promoter. SOX10 transactivates the EDNRB promoter through the cis-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 EDNRB promoter through these cis-acting elements. Furthermore, we have shown that the EDNRB promoter is heavily methylated in HeLa human cervical cancer cells, lacking EDNRB expression, but not in melanocytes and HMV-II melanoma cells. The expression of EDNRB 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 EDNRB gene, thereby ensuring appropriate expression level of EDNRB in human melanocytes.

Original languageEnglish
Pages (from-to)1805-1820
Number of pages16
JournalFEBS Journal
Volume273
Issue number8
DOIs
Publication statusPublished - 2006 Apr

Keywords

  • Endothelin receptor type B
  • Melanocytes
  • SOX10
  • Sp1
  • Waardenburg syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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