转录中介体复合物在心血管发育和疾病中的转录调控作用

doi:10.16288/j.yczz.21-411

遗传 ›› 2022, Vol. 44 ›› Issue (5): 383-397.doi: 10.16288/j.yczz.21-411

转录中介体复合物在心血管发育和疾病中的转录调控作用

张元¹(), 赵语婷¹, 庄乐南^1,^2,³(), 贺津³()

1. 浙江大学动物科学学院动物医学系,杭州 310058
2. 浙江大学医学院附属邵逸夫医院心内科,浙江省心血管介入与再生修复研究重点实验室,杭州 310016
3. 浙江大学动物科学学院动物遗传育种与繁殖研究所,杭州 310058

收稿日期:2022-01-18 修回日期:2022-03-03 出版日期:2022-05-20 发布日期:2022-03-28
通讯作者: 庄乐南,贺津 E-mail:zhangyuan2020@zju.edu.cn;hejin@zju.edu.cn
作者简介:张元,博士研究生,研究方向：转录调控。E-mail: zhangyuan2020@zju.edu.cn
基金资助:
国家重点研发计划编号(2019YFE0117400);国家重点研发计划,国家自然科学基金项目和中央高校基本科研业务费专项基金资助(2021YFA0805902);国家自然科学基金项目编号(81941003);中央高校基本科研业务费专项基金编号资助(2020XZZX002-20)

Transcriptional regulation of transcriptional Mediator complexes in cardiovascular development and disease

Yuan Zhang¹(), Yuting Zhao¹, Lenan Zhuang^1,^2,³(), Jin He³()

1. Department of Veterinary Medicine, College of Animal Science, Zhejiang University, Hangzhou 310058, China
2. Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Cardiovascular Intervention and Regeneration Medicine of Zhejiang Province, Hangzhou 310016, China
3. Institute of Animal Genetics, Breeding and Reproduction, College of Animal Science, Zhejiang University, Hangzhou 310058, China

Received:2022-01-18 Revised:2022-03-03 Online:2022-05-20 Published:2022-03-28
Contact: Zhuang Lenan,He Jin E-mail:zhangyuan2020@zju.edu.cn;hejin@zju.edu.cn
Supported by:
Supported by the National Key Research and Development Program Nos(2019YFE0117400);Supported by the National Key Research and Development Program Nos(2021YFA0805902);the National Natural Science Foundation of China(81941003);the Fundamental Research Funds for the Central Universities No(2020XZZX002-20)

摘要/Abstract

摘要：

哺乳动物心血管系统发育过程中,各分子、细胞和组织器官形态发生过程的精细协调对于形成成熟且功能齐全的心血管系统是不可或缺的,这些过程出现异常通常会导致严重的先天性心血管发育缺陷。多细胞生物中细胞命运的决定和维持在很大程度上依赖于对RNA聚合酶II (Pol II)转录活性的时空精确调控,而转录中介体(Mediator)在Pol II转录过程中起着重要的协同作用。Mediator是一种进化上保守的多亚基蛋白质复合体,包括头部、中部、尾部和激酶部四个部分,是转录因子和基础转录机器之间的功能联系的桥梁。近年来,鉴于Mediator在基因表达中的关键作用,越来越多的人类心血管疾病被证实与特定的Mediator基因突变相关,如心脏瓣膜缺陷、大动脉转位、DiGeorge综合征及一些与能量稳态失衡相关的心血管疾病。本文就Mediator在心血管系统发育和疾病中的作用进行综述,重点讨论Mediator对转录调控的影响在心血管疾病发生发展中的作用,旨在为与Mediator相关的心血管系统发育和疾病的研究提供广阔的研究思路。

关键词: 转录中介体复合物, 转录调控, 心血管系统发育, 心血管系统疾病

Abstract:

During the development of the mammalian cardiovascular system, the formation of a mature and fully functional cardiovascular system needs the fine coordination of the morphogenesis of various molecules, cells, tissues, and organs. Abnormalities in these processes usually lead to serious congenital heart defects. The determination and maintenance of cell fate in multicellular organisms depend to a large extent on the precise timing and control of RNA polymerase II (Pol II) transcription, and the transcription Mediator complex plays an irreplaceable role in the Pol II transcription process. Mediator is an evolutionarily conserved multi-subunit protein complex, including four parts: head, middle, tail, and kinase. It is a functional bridge between transcription factors and basic transcription machines. In recent years, due to the key role of Mediator in the transcriptional regulation of gene expression, many of human heart diseases have been confirmed to be related to specific Mediator gene mutations, such as heart valve defects, translocation of the great arteries, DiGeorge syndrome and some cardiovascular diseases related to energy homeostasis. In this review, we summarize the role of Mediator in cardiovascular development and disease, focusing on the role of Mediator in the development of cardiovascular disease, and provides a broad idea for the research on Mediator-related cardiovascular system development and diseases.

Key words: Mediator complex, transcriptional regulation, cardiovascular development, cardiovascular disease

张元, 赵语婷, 庄乐南, 贺津. 转录中介体复合物在心血管发育和疾病中的转录调控作用[J]. 遗传, 2022, 44(5): 383-397.

Yuan Zhang, Yuting Zhao, Lenan Zhuang, Jin He. Transcriptional regulation of transcriptional Mediator complexes in cardiovascular development and disease[J]. Hereditas(Beijing), 2022, 44(5): 383-397.

图/表 2

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亚基	心血管疾病	生物进程	研究对象	参考文献
MED1	薄心肌壁综合征	心肌壁、心肌小梁发育异常	人类	[59]
MED12	先天性心脏畸形	心血管系统发育缺陷	人类	[60]
MED13	代谢性心脏病	能量代谢障碍	小鼠	[61]
MED13L	大动脉转位	早期心脏发育缺陷	人类	[62,63]
MED15	DiGeorge综合征	心脏畸形	人类	[64,65]
MED23	心脏水肿、心率降低	血管平滑肌发育异常	斑马鱼	[66]
MED25	心室和(或)心房间隔缺损	MED25与Mediator间相互作用受损	人类	[67]
MED30	扩张性心肌病	心脏线粒体功能障碍	小鼠	[68]
CDK8	过表达导致进行性扩张型心肌病、心力衰竭	左心室心肌细胞显著延长、横管紊乱、钙处理功能障碍	小鼠	[69]

转录中介体复合物在心血管发育和疾病中的转录调控作用

Transcriptional regulation of transcriptional Mediator complexes in cardiovascular development and disease

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