染色质结构蛋白变异与人类疾病  

Variations in chromatin architectural proteins in human diseases

作　　者：曹红 吴迪 魏瑜 林海燕 李国红[1,2] CAO Hong;WU Di;WEI Yu;LIN HaiYan;LI GuoHong(National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;Frontier Science Centre of Immunology and Metabolism,TaiKang Center for Life and Medical Sciences,Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Wuhan University,Wuhan 430072,China)

机构地区：[1]中国科学院生物物理研究所,生物大分子国家重点实验室,北京100101 [2]武汉大学生命科学学院细胞稳态湖北省重点实验室,泰康生命医学中心,免疫与代谢前沿科学中心,武汉430072

出　　处：《中国科学：生命科学》2023年第11期1575-1594,共20页Scientia Sinica(Vitae)

基　　金：北京市科技计划项目(批准号:Z221100007022001);国家自然科学基金(批准号:32300435,32270581)资助。

摘　　要：层级复杂的三维染色质结构对于细胞命运决定和功能维持所需的多种DNA相关生物学过程的时空调控至关重要,如DNA复制、转录、重组和损伤修复等.三维染色质结构失调导致基因表达异常,被认为是肿瘤或神经发育障碍等多种疾病的主要诱因.本文重点阐述组蛋白及其变体、甲基CpG结合蛋白2在三维染色质高级结构及动态性调节中的作用,总结疾病相关突变对基因功能的影响,探讨肿瘤或神经发育障碍发生发展过程中染色质层面的病理学机制.The hierarchical three-dimensional(3D)chromatin architecture is central to spatiotemporal control of multiple biological processes inherent to DNA that are required for the maintenance of cell identity and function,including DNA replication,transcription,recombination,damage repair.Aberrant alterations in 3D chromatin architecture,which lead to pathological gene expression programmes,have been delineated as prominent causes of many diseases,such as tumors and neurodevelopmental disorders.In this review,we summarize the roles of histones,histone variants and methyl CpG-binding protein 2 in the regulation of 3D chromatin structure and dynamics,explore the impacts of human diseases-related mutations on their functions,and provide insights into the underlying pathological mechanisms of tumors and neurodevelopmental disorders from the aspect of chromatin structure.three-dimensional(3D)chromatin architecture,chromatin architectural proteins,histones and histone variants,

关 键 词：三维染色质结构 染色质结构蛋白 组蛋白及其变体 甲基CpG结合蛋白2(MeCP2) 人类疾病 

分 类 号：R394[医药卫生—医学遗传学]