Co-opted transposons help perpetuate conserved higher-order chromosomal structures

Area of Science:

• Genomics
• Epigenetics
• Evolutionary Biology

Background:

• Transposable elements (TEs) comprise half of mammalian genomes.
• TEs harbor regulatory factor binding sites, influencing genome regulation.
• Architectural proteins like CTCF, RAD21, and SMC3 bind TEs to tether chromatin loops and define domain boundaries.

Purpose of the Study:

• Investigate the role of TEs in the emergence and evolution of mammalian genome 3D organization.
• Determine how TEs contribute to conserved and species-specific genome structures.
• Explore the impact of TEs on genome plasticity and regulatory conservation.

Main Methods:

• Analysis of transposable elements in human and mouse genomes.
• Identification of CTCF binding sites within TEs.
• Experimental deletion of TEs in human cells.
• DNA methylation analysis and evolutionary mutational signature assessment.

Main Results:

• TEs contribute to species-specific loops via novel anchoring motifs.
• TEs maintain conserved loops through CTCF binding site turnover, acting as redundant anchors.
• Deletion of TEs causes collapse of conserved loop and domain structures.
• TEs show reduced DNA methylation and hypomethylation signatures over evolutionary time.

Conclusions:

• TEs drive regulatory plasticity by providing redundant anchors, promoting local genetic drift while conserving global genome architecture.
• TEs offer a new paradigm for understanding noncoding genome regulatory conservation beyond sequence similarity.
• TEs are critical for maintaining genome topology and function across species.