Regulatory transposable elements in the encyclopedia of DNA elements

• Published in: Nature communications Vol. 15; no. 1; pp. 7594 - 14
• Main Authors: Du, Alan Y., Chobirko, Jason D., Zhuo, Xiaoyu, Feschotte, Cédric, Wang, Ting
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45/15; 45/43; 631/208/200; 631/208/212; 631/208/212/177; 631/208/212/2304; 631/208/212/2305; Animals; Binding sites; Binding Sites - genetics; Deoxyribonucleic acid; DNA; DNA Transposable Elements - genetics; Evolution, Molecular; Genome, Human; Genomes; Humanities and Social Sciences; Humans; Mice; multidisciplinary; Regulatory sequences; Regulatory Sequences, Nucleic Acid - genetics; Science; Science (multidisciplinary); Transcription Factors - genetics; Transcription Factors - metabolism; Transposons
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51921-6

Transposable elements (TEs) comprise ~50% of our genome, but knowledge of how TEs affect genome evolution remains incomplete. Leveraging ENCODE4 data, we provide the most comprehensive study to date of TE contributions to the regulatory genome. We find 236,181 (~25%) human candidate cis-regulatory elements (cCREs) are TE-derived, with over 90% lineage-specific since the human-mouse split, accounting for 8–36% of lineage-specific cCREs. Except for SINEs, cCRE-associated transcription factor (TF) motifs in TEs are derived from ancestral TE sequence more than expected by chance. We show that TEs may adopt similar regulatory activities of elements near their integration site. Since human-mouse divergence, TEs have contributed 3–56% of TF binding site turnover events across 30 examined TFs. Finally, TE-derived cCREs are similar to non-TE cCREs in terms of MPRA activity and GWAS variant enrichment. Overall, our results substantiate the notion that TEs have played an important role in shaping the human regulatory genome. Half of our genome is transposable elements (TEs), often called junk DNA. Using the latest ENCODE data, the authors find TEs to contribute ~25% of human regulatory elements (REs). TEs can be adopted into new REs or replace old ones during evolution.