Characterization of sequence determinants of enhancer function using natural genetic variation.

ABSTRACT: Sequence variation in enhancers that control cell-type-specific gene transcription contributes significantly to phenotypic variation within human populations. However, it remains difficult to predict precisely the effect of any given sequence variant on enhancer function due to the complexity of DNA sequence motifs that determine transcription factor (TF) binding to enhancers in their native genomic context. Using F₁-hybrid cells derived from crosses between distantly related inbred strains of mice, we identified thousands of enhancers with allele-specific TF binding and/or activity. We find that genetic variants located within the central region of enhancers are most likely to alter TF binding and enhancer activity. We observe that the AP-1 family of TFs (Fos/Jun) are frequentl

SUBMITTER: Yang MG 

PROVIDER: S-EPMC9662815 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature