组蛋白去甲基化酶KDM7家族在脑疾病中研究进展

doi:10.16288/j.yczz.21-280

遗传 ›› 2022, Vol. 44 ›› Issue (1): 25-35.doi: 10.16288/j.yczz.21-280

组蛋白去甲基化酶KDM7家族在脑疾病中研究进展

杨卓瑾^1,^2,³(), 张玉向^1,^2,³(), 杨茜茜^1,^2,³, 高菲菲^1,^2,³, 杨婧思^1,^2,³, 阎春霞^1,^2,³()

1. 西安交通大学法医学院, 西安 710061
2. 国家卫生健康委员会法医学重点实验室(西安交通大学),西安 710061
3. 西安交通大学西部科技创新港生物证据研究院,西安 712000

收稿日期:2021-10-01 修回日期:2021-12-21 出版日期:2022-01-20 发布日期:2022-01-04
通讯作者: 张玉向,阎春霞 E-mail:cloris_sunshine@stu.xjtu.edu.cn;yuxiangzhang@xjtu.edu.cn;yanchunxia@mail.xjtu.edu.cn
作者简介:杨卓瑾,在读硕士研究生,专业方向：法医病理学及药物成瘾等脑疾病。E-mail: cloris_sunshine@stu.xjtu.edu.cn
基金资助:
国家自然科学基金项目编号(81971792);国家自然科学基金项目编号(81901920);中国博士后基金编号(2019M663746);陕西省自然科学研究计划项目资助编号(2020JQ-091)

The role of histone demethylases of KDM7 family in brain-related disorders

Zhuojin Yang^1,^2,³(), Yuxiang Zhang^1,^2,³(), Xixi Yang^1,^2,³, Feifei Gao^1,^2,³, Jingsi Yang^1,^2,³, Chunxia Yan^1,^2,³()

1. College of Forensic Medicine, Xi’an Jiaotong University, Xi’an 710061, China
2. Key Laboratory of National Health Commission for Forensic Medicine, Xi'an Jiaotong University, Xi'an 710061, China
3. Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an 712000, China

Received:2021-10-01 Revised:2021-12-21 Online:2022-01-20 Published:2022-01-04
Contact: Zhang Yuxiang,Yan Chunxia E-mail:cloris_sunshine@stu.xjtu.edu.cn;yuxiangzhang@xjtu.edu.cn;yanchunxia@mail.xjtu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China Nos(81971792);Supported by the National Natural Science Foundation of China Nos(81901920);the China Postdoctoral Science Foundation No(2019M663746);the Natural Science Basic Research Program of Shaanxi Province No(2020JQ-091)

摘要/Abstract

摘要：

组蛋白去甲基化酶KDM7家族包括KDM7A、KDM7B、KDM7C三种蛋白,主要通过去除与转录沉默相关的特定组蛋白赖氨酸甲基化修饰,进而对基因转录发挥调控作用。目前,对KDM7家族的研究主要集中于其在神经分化、肿瘤发生发展等过程中的作用,而对其在脑神经疾病中的作用却知之甚少。本文从该蛋白家族表观遗传调控机制、结构生物学及其在脑神经疾病中的作用等方面进行了综述,以期为研究其在脑神经疾病中的功能机制提供参考,为理解脑神经疾病分子病理机制以及探索基于该机制的有效治疗靶点带来新的启示。

关键词: 组蛋白去甲基化酶, KDM7, H3K9me2, H3K27me2

Abstract:

The histone demethylases of KDM7 family, including KDM7A, KDM7B and KDM7C, regulate transcription through acting on specific histone lysines. Previous studies have shown that these family members are functionally important for the processes of neural differentiation and tumor development, and little is known about their roles in brain neurological diseases. In this review, we summarize the latest research progress of KDM7 family on their epigenetic regulation mechanisms, their protein structures and their functions in brain-related diseases, which will likely advance our understanding of the molecular mechanisms of neurological diseases.

Key words: histone lysine demethylases, KDM7, H3K9me2, H3K27me2

杨卓瑾, 张玉向, 杨茜茜, 高菲菲, 杨婧思, 阎春霞. 组蛋白去甲基化酶KDM7家族在脑疾病中研究进展[J]. 遗传, 2022, 44(1): 25-35.

Zhuojin Yang, Yuxiang Zhang, Xixi Yang, Feifei Gao, Jingsi Yang, Chunxia Yan. The role of histone demethylases of KDM7 family in brain-related disorders[J]. Hereditas(Beijing), 2022, 44(1): 25-35.

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脑神经疾病	研究的组织	组蛋白修饰的改变		表型变化	参考文献
H3K4me3
智力障碍	小鼠胚胎、神经干细胞	↑(整体)	Ark基因敲除导致KDM5C下调,H3K4me3上调,消除REST介导的神经元基因调节	神经元功能障碍	[29]
自闭症	左侧海马	↓(Crhrl基因启动子区)	—	旷场实验认知行为异常	[30]
精神分裂症	内侧前额皮层(mPFC)	↓(整体及PV基因启动子区)	mPFC中H3K4me3总水平降低,PV、Gad1基因启动子区域结合的H3K4me3降低,导致PV mRNA和GAD67 mRNA水平降低	青年大鼠社会功能障碍	[31]
可卡因成瘾	伏隔核	↑(Nr4a1基因启动子区)	Nr4a1激活正向调节Cartpt表达和相关的组蛋白修饰	CPP增强	[32]
酒精成瘾	前额叶皮层	↓(整体)	—	酒精依赖	[33]
安非他明成瘾	伏隔核	↑(伏隔核整体及Oxtr和Fos基因启动子区)	KMD5C敲除导致H3K4me3升高	CPP增强	[34]
H3K9me2
智力障碍/ 自闭症	海马	↑(整体)	EHMT1下调,Pcdhs基因表达减少	神经认知功能受损	[35]
精神分裂症	大脑皮质及纹状体	↑(整体)	IL-6、Gad1等基因表达上调	认知功能异常	[36]
可卡因/吗啡/ 酒精成瘾	伏隔核	↑(整体)	G9a过表达抑制BDNF-trkB-CREB信号传导,增强H3K9me2介导的基因抑制	CPP减弱	[37~39]
H3K27me2
自闭症	老龄小鼠精子	↑(整体)	—	父系衰老诱发子代自闭症风险上调	[40]
酒精成瘾	海马及大脑皮质	↑(整体)	激活G9a可以抑制BDNF基因的转录及CREB的磷酸化等过程	神经退化	[41]

组蛋白去甲基化酶KDM7家族在脑疾病中研究进展

The role of histone demethylases of KDM7 family in brain-related disorders

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