Analysis of single-cell CRISPR perturbations indicates that enhancers act multiplicatively and provides limited evidence for epistatic-like interactions.

ABSTRACT: A single gene may have multiple enhancers, but how they work in concert to regulate transcription is poorly understood. To analyze enhancer interactions throughout the genome, we developed a generalized linear modeling framework, GLiMMIRS, for interrogating enhancer effects from single-cell CRISPR experiments. We applied GLiMMIRS to a published dataset and tested for interactions between 46,166 enhancer pairs and corresponding genes, including 264 'high-confidence' enhancer pairs. We found that enhancer effects combine multiplicatively but with limited evidence for further interactions. Only 31 enhancer pairs exhibited significant interactions (FDR < 0.1), of which none came from the high confidence subset and 20 were driven by outlier expression values. Additional analyses of a second CRI

SUBMITTER: Zhou J 

PROVIDER: S-EPMC10168320 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature