Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals.

ABSTRACT: Gene regulatory elements drive complex biological phenomena and their mutations are associated with common human diseases. The impacts of human regulatory variants are often tested using model organisms such as mice. However, mapping human enhancers to conserved elements in mice remains a challenge, due to both rapid enhancer evolution and limitations of current computational methods. We analyze distal enhancers across 45 matched human/mouse cell/tissue pairs from a comprehensive dataset of DNase-seq experiments, and show that while cell-specific regulatory vocabulary is conserved, enhancers evolve more rapidly than promoters and CTCF binding sites. Enhancer conservation rates vary across cell types, in part explainable by tissue specific transposable element activity. We present an improv

SUBMITTER: Oh JW 

PROVIDER: S-EPMC11291912 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature