Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Nat Rev Mol Cell Biol. 2022 Jul;23(7):481-497. doi: 10.1038/s41580-022-00457-y. Epub 2022 Feb 28.
Transposable elements (TEs) comprise about half of the mammalian genome. TEs often contain sequences capable of recruiting the host transcription machinery, which they use to express their own products and promote transposition. However, the regulatory sequences carried by TEs may affect host transcription long after the TEs have lost the ability to transpose. Recent advances in genome analysis and engineering have facilitated systematic interrogation of the regulatory activities of TEs. In this Review, we discuss diverse mechanisms by which TEs contribute to transcription regulation. Notably, TEs can donate enhancer and promoter sequences that influence the expression of host genes, modify 3D chromatin architecture and give rise to novel regulatory genes, including non-coding RNAs and transcription factors. We discuss how TEs spur regulatory evolution and facilitate the emergence of genetic novelties in mammalian physiology and development. By virtue of their repetitive and interspersed nature, TEs offer unique opportunities to dissect the effects of mutation and genomic context on the function and evolution of cis-regulatory elements. We argue that TE-centric studies hold the key to unlocking general principles of transcription regulation and evolution.
转座元件 (TEs) 约占哺乳动物基因组的一半。TEs 通常包含能够招募宿主转录机制的序列，这些序列可用于表达自身产物并促进转座。然而，TEs 失去转座能力后，其携带的调节序列可能会长期影响宿主转录。基因组分析和工程学的最新进展促进了对 TEs 调节活性的系统研究。在这篇综述中，我们讨论了 TEs 促进转录调控的多种机制。值得注意的是，TEs 可以捐赠增强子和启动子序列，影响宿主基因的表达，修饰 3D 染色质结构，并产生新的调控基因，包括非编码 RNA 和转录因子。我们讨论了 TEs 如何促进调控进化，并促进哺乳动物生理和发育中遗传新奇性的出现。由于其重复和分散的性质，TEs 为剖析突变和基因组背景对顺式调控元件功能和进化的影响提供了独特的机会。我们认为，以 TEs 为中心的研究是揭示转录调控和进化一般原理的关键。
