转座元件、表观遗传调控与细胞命运决定  

Epigenetic control of transposable elements and cell fate decision

作　　者：何江平 陈捷凯 Jiangping He;Jiekai Chen(Center for Cell Lineage and Atlas(CCLA),Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou 510530,China;Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China)

机构地区：[1]生物岛实验室细胞命运与谱系中心,广州510530 [2]中国科学院广州生物医药与健康研究院,广州510530

出　　处：《遗传》2021年第9期822-834,共13页Hereditas（Beijing)

基　　金：国家重点研发计划(编号:2019YFA0110200);中国科学院基础前沿科学研究计划0-1项目(编号:ZDBS-LY-SM007)。

摘　　要：转座元件是哺乳动物基因组内含量最多的元素。尽管转座元件的存在对基因组稳定性具有潜在的危险,但它们同时还是潜在的基因调控序列、蛋白质编码序列和染色质结构序列,并参与物种进化过程。因此,基因组中转座元件的有害性和有益性保持着谨慎的平衡,并且这种平衡主要由表观遗传修饰来调控。本文详细介绍了异染色质类型表观遗传修饰如H3K9me3和DNA甲基化在转座元件沉默中的功能;转座元件作为增强子元件富集激活型表观遗传修饰如H3K4me1和H3K27ac,以及作为转录因子结合靶点、染色质构象锚点等方式参与基因表达调控的模式;从体内胚胎发育到体外细胞命运转变,阐述了转座元件在细胞命运决定中的潜在功能及作用方式;最后,对转座元件领域研究存在的挑战及潜在解决方法提出了见解。总之,本文对转座元件与表观遗传、基因表达调控以及细胞命运决定等方面的研究及存在的问题进行了较全面的综述,旨在为相关领域的研究人员提供参考。Transposable elements(TEs)are the most prevalent elements in mammalian genomes.Although potential risks for genome stability,they are a pool of potential regulatory sequences,chromatin control elements,protein-coding genes,and substrates for evolutionary processes.Consequently,a delicate balance is maintained between the potential benefits and deleterious aspects of TEs,and this balance is mediated by the epigenetic regulatory system.In this review,we introduce the role of heterochromatin associated epigentic modifications such as histone 3 lysine 9 trimethylation(H3K9me3)and DNA methylation in the silencing of TEs as well as epigenetic modifications such as histone 3 lysine 4 monomethylation(H3K4me1)and histone 3 lysine 27 acetylation(H3K27ac)in activation of TEs.Further,we elaborate the functions of TEs as binding sites of transcription factors and as anchors of chromosomal conformation in regulation of gene expression.We introduce the impact of TEs on the process of cell fate determination including natural embryonic development in vivo and artificial cell fate transition in vitro.We discuss the main challenges associated with computational TEs analysis and TEs functions exploration,as well as the different experimental and computational strategies in studying these processes.In all,this article provides a comprehensive review of the research advances and existing problems in study of transposable elements in epigenetic regulatory mechanisms,gene transcriptional regulation,and cell fate determination,thereby providing some references for researchers in the fields.

关 键 词：转座元件 表观遗传调控 细胞命运决定 

分 类 号：Q343[生物学—遗传学]