Volume 20, No 7, Jul 2010
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 20 Issue 7, July 2010: 794-801
ORIGINAL ARTICLES
PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis
Ziqi Zhu1,2, Yanru Wang1,2,3, Xia Li1,2, Yiqin Wang1,2, Longyong Xu1,2, Xiang Wang2, Tianliang Sun2, Xiaobin Dong2, Lulu Chen2, Hailei Mao1,2,3, Yi Yu1,2, Jingsong Li2,4, Pin Adele Chen2 and Charlie Degui Chen1,2
1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 310 Yueyang Road, Shanghai 100031, China
2Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 310 Yueyang Road, Shanghai 100031, China
3Affiliated Hospital of Nantong University, Nantong 226001, China
4Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 310 Yueyang Road, Shanghai 100031, China
Correspondence: Pin Adele Chen, Charlie Degui Chen,(pinchen@sibs.ac.cn; cdchen@sibs.ac.cn)
Dimethylation of histone H3 lysine 9 (H3K9me2) is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.
Cell Research (2010) 20:794-801. doi: 10.1038/cr.2010.75; published online 8 June 2010
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