PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis  

作　　者：Ziqi Zhu Yanru Wang Xia Li Yiqin Wang Longyong Xu Xiang Wang Tianliang Sun Xiaobin Dong Lulu Chen Hailei Mao Yi Yu Jingsong Li Pin Adele Chen Charlie Degui Chen 

机构地区：[1]State 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 [2]Shanghai 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 [3]Affiliated Hospital of Nantong University, Nantong 226001, China [4]Laboratory 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

出　　处：《Cell Research》2010年第7期794-801,共8页细胞研究（英文版）

基　　金：Acknowledgments We thank the cell biology core facility for confocal study. The PHF8 antibody was kindly provided by Dr Jiemin Wong （East China Normal University）. This work was supported by the National Basic Research Program of China （2007CB947900, 2010CB529705, 2007CB947100）, the Chinese Academy of Sci- ences （KSCX2-YW-R-04, KSCX2-YW-R-I 11）, the National Natural Science Foundation of China （30870538, 90919026）, Postdoctoral fellowship （20090460670）, and the Council of Shanghai Municipal Government for Science and Technology.

摘　　要：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.

关 键 词：PHFS histone demethylase H3K9me2 rRNA synthesis 

分 类 号：Q987[生物学—遗传学] S511[生物学—人类学]