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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The authors thank members of the Wang laboratory for helpful discussions related to the project.
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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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DOI: https://doi.org/10.1038/s41576-023-00609-6