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J Biol Chem. 2010 Mar 5;285(10):7187-96. doi: 10.1074/jbc.M109.061861. Epub 2009 Dec 22.

Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors.

Author information

  • 1Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.

Abstract

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.

PMID:
20032463
[PubMed - indexed for MEDLINE]
PMCID:
PMC2844168
Free PMC Article

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