组蛋白去甲基化酶LSD1及其生物学功能.pdfVIP

HEREDITAS (Beijing) 2010 4 , 32(4): 331 ―338 ISSN 0253-9772 综述 DOI: 10.3724/SP.J.1005.2010.00331 组蛋白去甲基化酶LSD1 及其生物学功能 邵根宝, 黄晓佳, 龚爱华, 张志坚, 陆荣柱, 桑建荣 , 212013 赖氨酸特异性组蛋白去甲基化酶 1(Lysine specific demethylase 1, LSD1) 的发现, 表明组蛋白的甲基化 修饰是一个动态可调节的过程。结构分析显示, LSD1 是一个黄素腺嘌呤二核苷酸(Flavin adenine dinulcleotide, FAD) 依赖性胺氧化酶, 它能够特异性脱去单甲基化和二甲基化组蛋白H3 第4 位赖氨酸(H3K4) 和H3K9 位点 上的甲基基团。功能研究显示, LSD1 定位于细胞核内, 调控着基因转录的激活和抑制, 被誉为细胞深处的基因 “开关”, 在胚胎发育和肿瘤发生过程中起着重要的作用。文章主要综述了LSD1 的结构、作用机制及其调控 作用研究的新进展。 LSD1; 组蛋白去甲基化酶; 基因转录调控; 肿瘤抑制; 胚胎发育 Histone demethylase LSD1 and its biological functions SHAO Gen-Bao, HUANG Xiao-Jia, GONG Ai-Hua, ZHANG Zhi-Jian, LU Rong-Zhu, SANG Jian-Rong Institute of Basic Medical Science , School of Medicine, Jiangsu University , Zhenjiang 212013, China Abstract: Discovery of histone lysine specific demethylase 1 (LSD1) indicates that even histone methylation is reversible. Structural analysis shows that LSD1 is a flavin-dependent amine oxidase, which is able to catalyze the specific removal of methyl groups from mono- and dimethylated Lys4 and Lys9 of histone H3. Functional studies demonstrate that LSD1 regu- lates activation and inhibition of gene transcription in the nucleus, which is known as the innermost gene switch of cells. LSD1 plays important roles in embryonic development and tumorigenesis. Here, we review recent insights into the structure and chemical mechanism of LSD1, and its regulatory roles in development and cancer. Keywords: LSD1; histone demethylase; gene transcriptional regulation; cancer suppression; embryonic development , DNA , , 2004 , 147 bp DNA , 1 (Ly- H2AH2BH3 H4