tailieunhanh - Báo cáo khoa học: SOX10, in combination with Sp1, regulates the endothelin receptor type B gene in human melanocyte lineage cells

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 associ- | ềFEBS Journal SOX10 in combination with Sp1 regulates the endothelin receptor type B gene in human melanocyte lineage cells Satoru Yokoyama Kazuhisa Takeda and Shigeki Shibahara Department of Molecular Biology and Applied Physiology Tohoku University Schoolof Medicine Seiryo-machi Aoba-ku Sendai Miyagi Japan Keywords endothelin receptor type B melanocytes SOX10 Sp1 Waardenburg syndrome Correspondence K. Takeda Department of Molecular Biology and Applied Physiology Tohoku University Schoolof Medicine 2-1 Seiryo-machi Aoba-ku Sendai Miyagi 980-8575 Japan Fax 81 22 7178118 Tel 81 22 7178114 E-mail ktakeda@ Received 15 November 2005 revised 20 February 2006 accepted 27 February 2006 doi 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 .

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