Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.

ABSTRACT: The regulation of gene expression relies on the coordinated action of transcription factors (TFs) at enhancers, including both activator and repressor TFs. We employed deep learning (DL) to dissect HepG2 enhancers into positive (PAR), negative (NAR), and neutral activity regions. Sharpr-MPRA and STARR-seq highlight the dichotomy impact of NARs and PARs on modulating and catalyzing the activity of enhancers, respectively. Approximately 22% of HepG2 enhancers, termed "repressive impact enhancers" (RIEs), are predominantly populated by NARs and transcriptional repression motifs. Genes flanking RIEs exhibit a stage-specific decline in expression during late development, suggesting RIEs' role in trimming enhancer activities. About 16.7% of human NARs emerge from neutral rhesus macaque DNA. This

SUBMITTER: Song W 

PROVIDER: S-EPMC11761325 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature