《生命科学》 2012, 24(1): 7-12

赖氨酸特异性组蛋白去甲基化酶1作用机制及其生物学功能的研究进展

翟曜耀，刘晓霞，赵　越^*

(中国医科大学基础医学院，卫生部细胞生物学重点实验室，医学细胞生物学教育部重点实验室，染色质生物学研究室，沈阳 110001)

摘　要：摘　要：与其他化学修饰，如乙酰化、磷酸化、泛素化等相似，组蛋白赖氨酸甲基化是一个可以逆转的组蛋白修饰，是一个动态调节的过程。赖氨酸特异性组蛋白去甲基化酶1(lysine specific demethylase 1， 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H3K4和H3K9位点上的单甲基化和二甲基化的甲基基团。LSD1参与调控核受体介导的基因转录，并分别维持染色质的活性和非活性状态，被誉为细胞深处的基因“开关”。LSD1的功能失衡可引发多种重要生命现象的改变。主要综述LSD1的结构、作用机制及其在肿瘤发生、胚胎发育、体细胞重编程的调控、细胞分裂和造血等过程中生物学功能的研究新进展。
关键词：LSD1；基因转录调控；组蛋白去甲基化酶； 肿瘤抑制； 胚胎发育

Mechanism of LSD1 and its biological functions

ZHAI Yao-Yao， LIU Xiao-Xia， ZHAO Yue^*

(The Laboratory of Chromatin Biology， Department of Cell Biology， Key Laboratory of Public Health Ministry of China， Department of Medical Cell Biology of Ministry of Education， China Medical University， Shenyang 110001， China)

Abstract: Abstract: Histone lysine methylation is a reversible and dynamic process， which is same as that of other covalent histone modifications such as acetylation， phosphorylation and ubiquitylation. LSD1 is a flavin-dependent amine oxidase， and it is able to catalyze the specific removal of methyl groups from mono- and dimethylated Lys4 and Lys9 of histone H3. Functional studies have demonstrated that LSD1 is involved in nuclear receptor-mediated transcription， and individually maintenances active or inactive chromatin state. LSD1 is known as the innermost gene switch of cells. The imbalance of histone methylation and demethylation leads to alteration of many crucial life phenomena. This article reviews recent insights into the structure and mechanism of LSD1， and its biological functions in cancer， embryonic development， modulation of somatic cell reprogramming， cell division and hematopoiesis.
Key words: lysine specific demethylase 1; gene transcriptional regulation; histone demethylase; cancer suppression; embryonic development