失活X染色体基因逃逸与系统性红斑狼疮的性别二态性  

Genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus

作　　者：马茜[1,2] 周少岚 党洁[2,4] 霍正浩 马占兵[2,4] Qian Ma;Shaolan Zhou;Jie Dang;Zhenghao Huo;Zhanbing Ma(School of Life Sciences,Ningxia University,Yinchuan 750021,China;Department of Medical Genetics and Cell Biology,College of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;Department of Rheumatology,General Hospital of Ningxia Medical University,Yinchuan 750003,China;Key Laboratory of Fertility Preservation and Maintenance(Ningxia Medical University),Ministry of Education,Yinchuan 750004,China)

机构地区：[1]宁夏大学生命科学学院,银川750021 [2]宁夏医科大学基础医学院医学遗传学与细胞生物学系,银川750004 [3]宁夏医科大学总医院风湿免疫科,银川750003 [4]宁夏医科大学教育部生育力保持重点实验室,银川750004

出　　处：《遗传》2024年第1期18-33,共16页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:82060301,81960306);宁夏自然科学基金项目(编号:22KJB180014,2020AAC03116)资助。

摘　　要：X染色体失活可平衡女性中两条X染色体的基因剂量。越来越多的证据表明,失活X染色体上存在许多能够逃逸失活的基因。逃逸的机制涉及到DNA、RNA、组蛋白的表观修饰以及众多的调控蛋白和染色质的空间结构。失活X染色体基因逃逸的研究为人类疾病(特别是自身免疫性疾病)性别二态性的研究开辟了新的途径。目前已证实包括TLR7、CD40L、IRAK-1、CXCR3、CXorf21等失活X染色体基因逃逸是系统性红斑狼疮(systemic lupus erythematosus,SLE)女性好发的重要原因。本文主要综述了失活X染色体上基因逃逸以及与SLE性别二态性形成的分子机制。阐明SLE性别二态性形成的分子机制,不仅对疾病的诊断、治疗具有重要意义,而且对深入揭示人类免疫系统的发育及调控机理也有重要的理论意义。X chromosome inactivation can balance the effects of the two X chromosomes in females,and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation.The mechanisms of escape include modification of DNA,RNA,histone,epitope,and various regulatory proteins,as well as the spatial structure of chromatin.The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases,particularly autoimmune diseases.It has been demonstrated that the presence of TLR7,CD40L,IRAK-1,CXCR3,and CXorf21 significantly contributes to the prevalence of SLE(systemic lupus erythematosus)in females.This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus.Therefore,elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease,but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.

关 键 词：失活X染色体 基因 逃逸 性别二态性 系统性红斑狼疮 

分 类 号：R593.241[医药卫生—内科学]