Topologically associating domains are disrupted by evolutionary genome rearrangements forming species-specific enhancer connections in mice and humans.

ABSTRACT: Distinguishing between conserved and divergent regulatory mechanisms is essential for translating preclinical research from mice to humans, yet there is a lack of information about how evolutionary genome rearrangements affect the regulation of the immune response, a rapidly evolving system. The current model is topologically associating domains (TADs) are conserved between species, buffering evolutionary rearrangements and conserving long-range interactions within a TAD. However, we find that TADs frequently span evolutionary translocation and inversion breakpoints near genes with species-specific expression in immune cells, creating unique enhancer-promoter interactions exclusive to the mouse or human genomes. This includes TADs encompassing immune-related transcription factors, cytokine

SUBMITTER: Gilbertson SE 

PROVIDER: S-EPMC9142060 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature