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Transposable elements in mammalian chromatin organization

Nature Reviews Genetics volume 24, pages 712–723 (2023)Cite this article

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Abstract

Transposable elements (TEs) are mobile DNA elements that comprise almost 50% of mammalian genomic sequence. TEs are capable of making additional copies of themselves that integrate into new positions in host genomes. This unique property has had an important impact on mammalian genome evolution and on the regulation of gene expression because TE-derived sequences can function as cis-regulatory elements such as enhancers, promoters and silencers. Now, advances in our ability to identify and characterize TEs have revealed that TE-derived sequences also regulate gene expression by both maintaining and shaping 3D genome architecture. Studies are revealing how TEs contribute raw sequence that can give rise to the structures that shape chromatin organization, and thus gene expression, allowing for species-specific genome innovation and evolutionary novelty.

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Fig. 1: Different scales of 3D genome architecture.
Fig. 2: The many roles of TEs in chromatin organization.
Fig. 3: TEs contribute to maintenance of chromatin structures and to lineage-specific enhancer–promoter loops.
Fig. 4: TEs can contribute to TAD boundary diversity among individuals and cell types within an individual.
Fig. 5: TEs are central to short-range and long-range interactions.
Fig. 6: TEs affect heterochromatin assembly and organization.

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Acknowledgements

The authors thank members of the Wang laboratory for helpful discussions related to the project.

Author information

Authors and Affiliations

  1. Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA

    Heather A. Lawson, Yonghao Liang & Ting Wang

  2. Center for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, MO, USA

    Yonghao Liang & Ting Wang

  3. McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO, USA

    Ting Wang

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  1. Heather A. Lawson
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  2. Yonghao Liang
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  3. Ting Wang
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All authors researched data for the manuscript and reviewed/edited the manuscript before submission. H.A.L and T.W discussed the content and wrote the manuscript.

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Correspondence to Heather A. Lawson or Ting Wang.

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Nature Reviews Genetics thanks Juan Vaquerizas, who co-reviewed with Maria Rigau; Kenji Ichiyanagi; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

A and B compartments

Spatial compartments in which chromosomes are organized. The A compartment broadly correlates with transcriptionally active euchromatic regions, whereas the B compartment broadly correlates with transcriptionally inactive heterochromatic regions.

CCCT-C binding factor

(CTCF). A DNA binding protein that is essential for many cellular processes, including chromatin organization.

Chromosomal territories

Distinct regions of a cell’s nuclear volume that are occupied by each chromosome.

Cohesin

A multiprotein complex that is integral for loop extrusion and formation of topologically associating domain (TAD) boundaries.

DNA transposons

Transposable elements (TEs) that replicate through a cut-and-paste mechanism whereby the element is excised and moved to a different genomic location. DNA transposons are referred to as class II TEs.

Exaptation

When a trait or sequence evolves to function in a manner that is different from the function it originally served.

Insulator elements

DNA sequence motifs that either prevent enhancers from acting on a corresponding promoter or shield genes from the spread of heterochromatin that silences gene expression. In mammals, insulators frequently bind CTCF, often in association with the cohesin complex, and help organize distinct chromatin domains.

Long terminal repeat

(LTR). A class I retrotransposon that is characterized by LTRs flanking an internal coding sequence. LTRs comprise 8% of the human genome.

Phase separation

A mechanism by which genomic compartments with distinct chromatin states are formed. Phase separation refers to the formation of two distinct phases of a solution.

Retrotransposons

Transposable elements (TEs), including long terminal repeats (LTRs), long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), that replicate through a copy-and-paste mechanism: an RNA intermediate is reverse transcribed into cDNA and integrated into the genome. Retrotransposons are referred to as class I TEs.

Topologically associating domains

(TADs). Structures that are delimited by boundary elements, and that contain sequences that preferentially interact with themselves rather than with other genomic regions.

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Lawson, H.A., Liang, Y. & Wang, T. Transposable elements in mammalian chromatin organization. Nat Rev Genet 24, 712–723 (2023). https://doi.org/10.1038/s41576-023-00609-6

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