Roles of Transposable Elements in the Regulation of Mammalian Transcription

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2022 Mar 1

PMID 35228718

Authors

Raquel Fueyo

Julius Judd

Cedric Feschotte

Joanna Wysocka

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Association of a 7.9 kb Endogenous Retrovirus Insertion in Intron 1 of CD36 with Obesity and Fat Measurements in Sheep.

Saleh A, Moawad A, Yang N, Zheng Y, Chen C, Wang X Mob DNA. 2025; 16(1):12.

PMID: 40087777 DOI: 10.1186/s13100-025-00349-w.

Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.

Elder E, Lemieux A, Legault L, Caron M, Bertrand-Lehouillier V, Dupas T Nucleic Acids Res. 2025; 53(4).

PMID: 39997223 PMC: 11851107. DOI: 10.1093/nar/gkaf130.

Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.

Singh M, Leddy S, Iniguez L, Bendall M, Nixon D, Feschotte C Genome Biol. 2025; 26(1):28.

PMID: 39988678 PMC: 11849351. DOI: 10.1186/s13059-025-03484-y.

Massively parallel assessment of gene regulatory activity at human cortical structure associated variants.

Matoba N, McAfee J, Krupa O, Bell J, Le B, Valone J bioRxiv. 2025; .

PMID: 39974944 PMC: 11839127. DOI: 10.1101/2025.02.08.635393.

PIF/harbinger transposon-derived protein promotes 7SL expression to enhance pathogen resistance.

Geng S, Lv X, Xu T EMBO Rep. 2025; 26(5):1196-1211.

PMID: 39885293 PMC: 11893794. DOI: 10.1038/s44319-025-00379-8.

References

Wells J, Feschotte C . A Field Guide to Eukaryotic Transposable Elements. Annu Rev Genet. 2020; 54:539-561. PMC: 8293684. DOI: 10.1146/annurev-genet-040620-022145. View

Chuong E, Elde N, Feschotte C . Regulatory activities of transposable elements: from conflicts to benefits. Nat Rev Genet. 2016; 18(2):71-86. PMC: 5498291. DOI: 10.1038/nrg.2016.139. View

Fort V, Khelifi G, Hussein S . Long non-coding RNAs and transposable elements: A functional relationship. Biochim Biophys Acta Mol Cell Res. 2020; 1868(1):118837. DOI: 10.1016/j.bbamcr.2020.118837. View

Ozata D, Gainetdinov I, Zoch A, OCarroll D, Zamore P . PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 2018; 20(2):89-108. DOI: 10.1038/s41576-018-0073-3. View

Jangam D, Feschotte C, Betran E . Transposable Element Domestication As an Adaptation to Evolutionary Conflicts. Trends Genet. 2017; 33(11):817-831. PMC: 5659911. DOI: 10.1016/j.tig.2017.07.011. View

Pickar-Oliver A, Gersbach C . The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019; 20(8):490-507. PMC: 7079207. DOI: 10.1038/s41580-019-0131-5. View

Goodwin S, McPherson J, McCombie W . Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet. 2016; 17(6):333-51. PMC: 10373632. DOI: 10.1038/nrg.2016.49. View

Goerner-Potvin P, Bourque G . Computational tools to unmask transposable elements. Nat Rev Genet. 2018; 19(11):688-704. DOI: 10.1038/s41576-018-0050-x. View

McGuire A, Gabriel S, Tishkoff S, Wonkam A, Chakravarti A, Furlong E . The road ahead in genetics and genomics. Nat Rev Genet. 2020; 21(10):581-596. PMC: 7444682. DOI: 10.1038/s41576-020-0272-6. View

10.

Britten R, Davidson E . Gene regulation for higher cells: a theory. Science. 1969; 165(3891):349-57. DOI: 10.1126/science.165.3891.349. View

11.

Davidson E, Britten R . Regulation of gene expression: possible role of repetitive sequences. Science. 1979; 204(4397):1052-9. DOI: 10.1126/science.451548. View

12.

Feschotte C . Transposable elements and the evolution of regulatory networks. Nat Rev Genet. 2008; 9(5):397-405. PMC: 2596197. DOI: 10.1038/nrg2337. View

13.

Lander E, Linton L, Birren B, Nusbaum C, Zody M, Baldwin J . Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822):860-921. DOI: 10.1038/35057062. View

14.

Pehrsson E, Choudhary M, Sundaram V, Wang T . The epigenomic landscape of transposable elements across normal human development and anatomy. Nat Commun. 2019; 10(1):5640. PMC: 6904449. DOI: 10.1038/s41467-019-13555-x. View

15.

Bourque G, Leong B, Vega V, Chen X, Lee Y, Srinivasan K . Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res. 2008; 18(11):1752-62. PMC: 2577865. DOI: 10.1101/gr.080663.108. View

16.

Sundaram V, Cheng Y, Ma Z, Li D, Xing X, Edge P . Widespread contribution of transposable elements to the innovation of gene regulatory networks. Genome Res. 2014; 24(12):1963-76. PMC: 4248313. DOI: 10.1101/gr.168872.113. View

17.

Kunarso G, Chia N, Jeyakani J, Hwang C, Lu X, Chan Y . Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet. 2010; 42(7):631-4. DOI: 10.1038/ng.600. View

18.

Sundaram V, Choudhary M, Pehrsson E, Xing X, Fiore C, Pandey M . Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus. Nat Commun. 2017; 8:14550. PMC: 5379053. DOI: 10.1038/ncomms14550. View

19.

Wang T, Zeng J, Lowe C, Sellers R, Salama S, Yang M . Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A. 2007; 104(47):18613-8. PMC: 2141825. DOI: 10.1073/pnas.0703637104. View

20.

Hermant C, Torres-Padilla M . TFs for TEs: the transcription factor repertoire of mammalian transposable elements. Genes Dev. 2021; 35(1-2):22-39. PMC: 7778262. DOI: 10.1101/gad.344473.120. View