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Function and Constraint in Enhancer Sequences with Multiple Evolutionary Origins.


ABSTRACT: Thousands of human gene regulatory enhancers are composed of sequences with multiple evolutionary origins. These evolutionarily "complex" enhancers consist of older "core" sequences and younger "derived" sequences. However, the functional relationship between the sequences of different evolutionary origins within complex enhancers is poorly understood. We evaluated the function, selective pressures, and sequence variation across core and derived components of human complex enhancers. We find that both components are older than expected from the genomic background, and complex enhancers are enriched for core and derived sequences of similar evolutionary ages. Both components show strong evidence of biochemical activity in massively parallel report assays. However, core and derived sequences

SUBMITTER: Fong SL 

PROVIDER: S-EPMC9673499 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature