Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations.

ABSTRACT: Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also

SUBMITTER: Tjalsma SJD 

PROVIDER: S-EPMC11960515 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature