组蛋白修饰在先天性心脏病中的作用  

Role of Histone Modifications in the Congenital Heart Disease

作　　者：李璐 李建婷[1,2,3] LI Lu;LI Jian-Ting(Department of Biochemistry and Molecular Biology;Shanxi Key Laboratory of Birth Defect and Cell Regeneration;MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention;The Transformation Pilot-Base of Shanxi Clinical Cell Therapy,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院生物化学与分子生物学教研室 [2]山西医科大学出生缺陷与细胞再生山西省重点实验室 [3]山西医科大学煤炭环境致病与防治教育部重点实验室 [4]山西医科大学山西省临床级细胞治疗转化中试基地,太原030001

出　　处：《中国生物化学与分子生物学报》2024年第5期588-597,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.U23A20420,No.82201841);山西省基础研究计划(No.202203021212369);山西医科大学博士启动基金项目(No.SD2209,No.XD2116)资助。

摘　　要：先天性心脏病(congenital heart disease,CHD)是包括心肌壁、瓣膜和主要血管缺陷在内的心脏先天性结构异常疾病。虽然胚胎发生过程中的基因突变和异常基因表达等遗传因素会导致CHD,但这些只能解释一部分CHD的发病原因。表观遗传中的组蛋白修饰在CHD中的研究越来越多,提示其在CHD发病机制中愈发重要。随着基于质谱的蛋白质组学技术发展,一系列新型组蛋白翻译后修饰,包括琥珀酰化、糖基化、乳酸化和β-羟基丁酰化等在疾病中发挥的作用被揭示,而这些新型修饰如何调控CHD的发生发展过程中的基因表达以及病理进程并不得知。本文将分别从经典组蛋白修饰和新型组蛋白修饰出发阐述不同的组蛋白修饰参与调控心脏发育基因的作用机制,以期揭示组蛋白驱动的表观遗传机制在CHD病因学中的重要性,也为CHD的临床治疗及时预防提供理论依据。Congenital heart disease(CHD)refers to congenital structural abnormalities of the heart,including defects in the myocardial wall,valves,and major blood vessels.While genetic factors such as mutations and aberrant gene expression during embryogenesis contribute to CHD,they only account for part of cases.There are more and more studies on epigenetic histone modifications in CHD,suggesting that they are increasingly important in the pathogenesis of CHD.With the development of mass spectrometry-based proteomics technology,a spectrum of novel histone post-translational modifications,such as succinylation,glycosylation,lactylation,andβ-hydroxybutyrylation,have been uncovered to contribute to various diseases.However,it remains unclear how these novel modifications regulate gene expression and pathological processes during the development and progression of CHD.This article will delve into the mechanisms of various histone modifications that regulate genes associated with cardiac development.It will approach the topic from both the perspective of classic histone modifications and novel histone modifications,aiming to unveil the significance of histone-driven epigenetic mechanisms in the etiology of CHD.Furthermore,it seeks to offer insights into the etiology of CHD,providing a theoretical basis for clinical treatment and timely prevention of this condition.

关 键 词：组蛋白修饰 先天性心脏病 表观遗传 

分 类 号：Q11[生物学—普通生物学] R34[医药卫生—基础医学]