The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B

作     者：Yan Zhang Huirong Yang Xue Guo Naiyan Rong Yujiao Song Youwei Xu Wenxian Lan Xu Zhang Maili Liu Yanhui Xu Chunyang Cao 

作者机构：State Key Laboratory of Bio-organic and Natural Product Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China Institutes of Biomedical Sciences Fudan University 130 Dong-An Road Shanghai 200032 China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan 430071 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2014年第5卷第11期

页      面：837-850页

核心收录：

学科分类：0710[理学-生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 09[农学] 071007[理学-遗传学] 070303[理学-有机化学] 0901[农学-作物学] 0703[理学-化学] 090102[农学-作物遗传育种] 

基　　金：supported by funding from the National Basic Research Program of China from National Science Foundation of China 上海市浦江人才计划项目 

主　　题：KDM5B PHD1 H3K4me0 demethylase,repression structure 

摘      要：KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHDIKDMSB interacts with unmethylated H3K4me0. Our NMR structure of PHDIKDMSB in complex with H3K4me0 revealed that the binding mode is slightly different from that of other reported PHD fingers. The disruption of this interaction by double mutations on the residues in the interface （L325A/D328A） decreases the H3K4me2/3 demethylation activity of KDM5B in cells by approximately 50% and increases the transcriptional repression of tumor suppressor genes by approximately twofold. These findings imply that PHDIKDMSB may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B.