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標題: Histone Deacetylase 10 Relieves Repression on the Melanogenic Program by Maintaining the Deacetylation Status of Repressors
作者: Lai, I.L.
Lin, T.P.
Yao, Y.L.
Lin, C.Y.
Hsieh, M.J.
Yang, W.M.
關鍵字: waardenburg-syndrome;transcription factor;in-vivo;pax3;genes;acetylation;expression;protein;hdac10;microphthalmia
Project: Journal of Biological Chemistry
期刊/報告no:: Journal of Biological Chemistry, Volume 285, Issue 10, Page(s) 7187-7196.
HDAC10 belongs to the class II histone deacetylase family; however, its functions remain enigmatic. We report here that the HDAC10 protein complex contained deacetylated chaperone protein hsc70, and HDAC10 relieved repression of melanogenesis by decreasing the repressional activity of two transcriptional regulators, paired box protein 3 (Pax3) and KRAB-associated protein 1 (KAP1). HDAC10 physically interacted with Pax3 and KAP1 in a ternary complex and maintained Pax3 and KAP1 in a deacetylated state. Deacetylated Pax3 and KAP1 derepressed promoters of microphthalmia-associated transcription factor (MITF) and melanocyte-specific tyrosinase-related protein 1 and 2 (TRP-1 and TRP-2), three genes of the melanogenesis cascade, in a trichostatin A-sensitive manner. Co-occupancy of melanogenic promoters by HDAC10, Pax3, and KAP1 only happened in cells of the melanocyte lineage, and KAP1 facilitated nuclear enrichment of HDAC10. Finally, cellular melanin content correlated directly with the expression level and activity of HDAC10. Our results not only show that HDAC10 regulates melanogenesis but also demonstrate that the transcriptional activities of Pax3 and KAP1 are intimately linked to their acetylation status.
ISSN: 0021-9258
DOI: 10.1074/jbc.M109.061861
Appears in Collections:分子生物學研究所

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