遗传 ›› 2021, Vol. 43 ›› Issue (9): 822-834.doi: 10.16288/j.yczz.21-113

• 优博专栏 • 上一篇    下一篇

转座元件、表观遗传调控与细胞命运决定

何江平1,2, 陈捷凯1,2()   

  1. 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
  • 收稿日期:2021-03-25 修回日期:2021-07-23 出版日期:2021-09-20 发布日期:2021-08-19
  • 通讯作者: 陈捷凯 E-mail:chen_jiekai@gibh.ac.cn
  • 作者简介:何江平,博士,研究方向:转座元件的表观遗传调控及功能。E-mail: he_jiangping@grmh-gdl.cn
    2014—2019年就读于中国科学院广州生物医药与健康研究院,在陈捷凯课题组攻读博士学位,目前任生物岛实验室副研究员。博士期间,主要研究转座元件的表观遗传调控机制及其在细胞命运决定中的功能。利用生物信息学方法系统性解析了小鼠胚胎干细胞中所有转座元件的表观遗传修饰图谱,发现不同转座元件存在多种不同的表观遗传修饰调控模式,包括抑制型的H3K9me3和激活型的H3K27ac、H3K4me1等,并进一步筛选到了调控胚胎干细胞往2细胞样细胞重编程的新型调控因子。此外,还研究了转座元件LTR6B在人定型内胚层分化及转座元件RLTR13B2在小鼠上胚层干细胞往胚胎干细胞重编程等细胞命运决定中的功能及机制。博士论文《转座元件表观遗传调控与细胞命运决定》获得2020年中国科学院优秀博士生论文。截止目前,以第一作者(含共同)在Nature、Cell、Nature Cell Biology、Nature Communications和Protein & Cell等杂志发表论文8篇,以其他作者身份发表论文10篇,累积引用超过600次。
  • 基金资助:
    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)

Epigenetic control of transposable elements and cell fate decision

He Jiangping1,2, Chen Jiekai1,2()   

  1. 1. Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510530, China
    2. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;
  • Received:2021-03-25 Revised:2021-07-23 Online:2021-09-20 Published:2021-08-19
  • Contact: Chen Jiekai E-mail:chen_jiekai@gibh.ac.cn
  • Supported by:
    Supported by the National Key R&D Program of China No(2019YFA0110200);the Frontier Science Research Program of the CAS No(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。

关键词: 转座元件, 表观遗传调控, 细胞命运决定

Abstract:

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.

Key words: transposable elements, epigenetic regulation, cell fate decision