Sundaram Vasavi, Wysocka Joanna
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.
Philos Trans R Soc Lond B Biol Sci. 2020 Mar 30;375(1795):20190347. doi: 10.1098/rstb.2019.0347. Epub 2020 Feb 10.
Eukaryotic gene regulation is mediated by -regulatory elements, which are embedded within the vast non-coding genomic space and recognized by the transcription factors in a sequence- and context-dependent manner. A large proportion of eukaryotic genomes, including at least half of the human genome, are composed of transposable elements (TEs), which in their ancestral form carried their own -regulatory sequences able to exploit the host environment to promote TE transcription and facilitate transposition. Although not all present-day TE copies have retained this regulatory function, the preexisting regulatory potential of TEs can provide a rich source of -regulatory innovation for the host. Here, we review recent evidence documenting diverse contributions of TE sequences to gene regulation by functioning as enhancers, promoters, silencers and boundary elements. We discuss how TE-derived enhancer sequences can rapidly facilitate changes in existing gene regulatory networks and mediate species- and cell-type-specific regulatory innovations, and we postulate a unique contribution of TEs to species-specific gene expression divergence in pluripotency and early embryogenesis. With advances in genome-wide technologies and analyses, systematic investigation of TEs' -regulatory potential is now possible and our understanding of the biological impact of genomic TEs is increasing. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'.
真核基因调控由调控元件介导，这些元件嵌入在广阔的非编码基因组空间中，并被转录因子以序列和上下文依赖的方式识别。包括至少一半人类基因组在内的很大一部分真核基因组由转座元件（TEs）组成，这些转座元件在其原始形式中携带自身的调控序列，能够利用宿主环境促进TE转录并促进转座。虽然并非所有现存的TE拷贝都保留了这种调控功能，但TEs预先存在的调控潜力可为宿主提供丰富的调控创新来源。在这里，我们综述了最近的证据，这些证据记录了TE序列通过作为增强子、启动子、沉默子和边界元件对基因调控的多种贡献。我们讨论了TE衍生的增强子序列如何能够迅速促进现有基因调控网络的变化并介导物种和细胞类型特异性的调控创新，并且我们推测TEs对多能性和早期胚胎发生中物种特异性基因表达差异有独特贡献。随着全基因组技术和分析的进步，现在有可能对TEs的调控潜力进行系统研究，并且我们对基因组TEs的生物学影响的理解正在增加。本文是“转座子与基因调控的交叉点”讨论会议题的一部分。
