biostudies-literatureChoudhary MNKNIEHS NIH HHSNHGRI NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health634https://www.ebi.ac.uk/biostudies/studies/S-EPMC9902604biostudies-literatureUnknown14(1)Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific families and subfamilies of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate sustained interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to shaping 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.Nature communicationsWidespread contribution of transposable elements to the rewiring of mammalian 3D genomes.PMC9902604U24ES026699U24 ES026699U01HG009391U01 HG009391U01 CA200060UM1 HG011585U01CA200060P30 CA091842T32HG000045-18UM1HG011585R01 HG007175R01HG007175T32 HG000045Choudhary MNKQuaid KXing XWang TSchmidt HfalseWidespread contribution of transposable elements to the rewiring of mammalian 3D genomes.Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific families and subfamilies of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate sustained interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to shaping 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.2023-01-01T00:00:00Z2023 Feb2026-05-28T18:58:03.452Z2025-02-19T00:12:12.839ZS-EPMC99026043674694010.1038/s41467-023-36364-9