AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function  

作　　者：Ze Yang Jun Jiang David M Stewart Shankang Qi Kenichi Yamane Jiwen Li Yi Zhang Jiemin Wong 

机构地区：[1]The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China [2]Department of Urology, Daping Hospital/Institute of Surgical Research, Third Military Medical University, Chongqing 400042, China [3]Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [4]Howard Hughes Medical Institute and University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

出　　处：《Cell Research》2010年第3期276-287,共12页细胞研究（英文版）

基　　金：We thank Dr Ramin Shiekhattar （Wistar Institute, USA） for the baculoviruses expressing Flag-LSD1 and Drs Jianguo Song and Degui Chen （Shanghai Institute of Biochemistry and Cell Biol- ogy, China） for anti-HDAC1 antibody and H3K36me2 antibody, respectively. This study was partially supported by grants from the National Natural Science Foundation of China （90919025, 30871381）, the Ministry of Science and Technology of China （2009CB918402, 2009CB825601） and the Research Platform for Cell Signaling Networks from the Science and Technology Com- mission of Shanghai Municipality （06DZ22923）.

摘　　要：LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.

关 键 词：AOF1 histone H3K4 demethylase CHROMATIN REPRESSION Zf-CW 

分 类 号：S435.622.9[农业科学—农业昆虫与害虫防治] Q343.2[农业科学—植物保护]