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浙江大学学报（医学版）
浙江大学学报（医学版）  2022, Vol. 51 Issue (2): 251-260    DOI: 10.3724/zdxbyxb-2021-0192
综述     
甲基转移酶SET结构域家族及其在心血管发育和疾病中的作用
邢敬慈1,揭伟1,2,*()
1.广东医科大学基础医学院病理学系，广东 湛江 524023
2.海南医学院 急救与创伤研究教育部重点实验室 海南省热带心血管病研究重点实验室，海南 海口 571199
Methyltransferase SET domain family and its relationship with cardiovascular development and diseases
XING Jingci1,JIE Wei1,2,*()
1. Department of Pathology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China;
2. Hainan Medical University, Key Laboratory of Emergency and Trauma, Ministry of Education, Hainan Provincial Key Laboratory of Tropical Cardiovascular Diseases Research, Haikou 571199, China
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摘要：

表观遗传修饰异常与心血管疾病的发生、发展密切相关。SET结构域（SETD）家族是一类含有SETD的重要表观遗传修饰酶，主要通过修饰组蛋白H3K4、H3K9、H3K36和H4K20的甲基化而影响基因表达; 也可以催化非组蛋白的甲基化而影响信号转导及转录活化因子1、Wnt/β-catenin、缺氧诱导因子1α和Hippo/YAP等重要信号途径的信号转导。SETD家族对心血管发育和疾病的作用主要体现在以下几个方面：调控冠状动脉的形成和心脏发育；保护缺血再灌注损伤的心脏组织；调控糖尿病心血管并发症中的炎症反应、氧化应激和细胞凋亡；参与肺动脉高压形成；调控血栓形成、心肌肥大和心律失常等。本文综述了SETD家族成员的组成、表达调控机制及其在心血管发育和疾病中的作用研究进展，以期为深入理解心血管疾病发生和发展的分子机制及治疗靶点提供参考。
关键词： 表观遗传学;  甲基转移酶;  SET结构域;  心血管发育;  心血管疾病;  综述    
Abstract:

Abnormal epigenetic modification is closely related to the occurrence and development of cardiovascular diseases. The SET domain (SETD) family is an important epigenetic modifying enzyme containing SETD. They mainly affect gene expression by methylating H3K4, H3K9, H3K36 and H4K20. Additionally, the SETD family catalyzes the methylation of non-histone proteins, thereby affects the signal transduction of signal transduction and activator of transcription (STAT) 1, Wnt/β-catenin, hypoxia-inducible factor (HIF)-1α and Hippo/YAP pathways. The SETD family has the following regulatory effects on cardiovascular development and diseases: regulating coronary artery formation and cardiac development; protecting cardiac tissue from ischemia reperfusion injury; regulating inflammation, oxidative stress and apoptosis in cardiovascular complications of diabetes; participating in the formation of pulmonary hypertension; regulating thrombosis, cardiac hypertrophy and arrhythmia. This article summarizes the basic structures, expression regulation mechanisms and the role of existing SETD family members in cardiovascular development and diseases, in order to provide a basis for understanding the molecular mechanism of cardiovascular disease and exploring the therapeutic targets.
Key words: Epigenetics    Methyltransferase    SET domain    Cardiovascular development    Cardiovascular diseases    Review
收稿日期: 2021-07-07 出版日期: 2022-08-02
CLC:  R54  
基金资助: 国家自然科学基金（82060053）；广东省“扬帆计划”高层次人才项目（4YF16007G）
通讯作者: 揭伟     E-mail: wei_jie@hainmc.edu.cn
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引用本文:

邢敬慈,揭伟. 甲基转移酶SET结构域家族及其在心血管发育和疾病中的作用[J]. 浙江大学学报（医学版）, 2022, 51(2): 251-260.

XING Jingci,JIE Wei. Methyltransferase SET domain family and its relationship with cardiovascular development and diseases. J Zhejiang Univ (Med Sci), 2022, 51(2): 251-260.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0192    或    https://www.zjujournals.com/med/CN/Y2022/V51/I2/251

简称

全称

其他名称

染色体位置

组蛋白修饰位点

SETD1A

SET domain containing1A

KIAA0339、SET1、KMT2F

16p11.2

H3K4[10]

SETD1B

SET domain containing1B

KIAA1076、SET1B、KMT2G

12q24.31

H3K4[11]

SETD2

SET domain containing2

HYPB、HIF-1、KIAA1732、FLJ23184、KMT3A

3p21.31

H3K36[12]

SETD3

SET domain containing3

FLJ23027、C14orf154

14q32.2

—

SETD4

SET domain containing4

C21orf18、C21orf27

21q22.12

H4K20、H3K4[13-14]

SETD5

SET domain containing5

FLJ10707、KIAA1757

3p25.3

H3K36[15]

SETD6

SET domain containing6

FLJ21148

16q21

H3K9[16]

SETD7

SET domain containing7

KIAA1717、SET7、SET7/9、SET9、KMT7

4q31.1

H3K4[17]

SETD8

SET domain containing8

SET8、SET07、PR-SET7、KMT5A

12q24.31

H4K20[18]

SETD9

SET domain containing9

MGC33648、C5orf35

5q11.2

—
表 1  SETD家族成员基本信息一览
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