Quantifying the impact of genetic mutations on enhancer dynamics.

ABSTRACT: Transcriptional regulation is mediated by enhancers, yet how genetic perturbations alter enhancer activity and gene expression remains poorly understood. We developed UDI-UMI-STARR-seq, which integrates dual indexes and unique molecular identifiers, and combined it with RNA-seq to profile the effects of perturbations on enhancer activity and target gene expression. We applied this approach to a library of 253,632 fragments representing 46,142 cell type-specific candidate enhancers and assessed the impact of CRISPR/Cas9-mediated deletion of six transcription factors (or TFs; ATF2, CTCF, FOXA1, LEF1, TCF7L2, and SCRT1) with diverse regulatory roles. Across knockout lines, we identified responsive enhancers that were either repressed or induced, often through motifs such as the p53 family of

SUBMITTER: Das M 

PROVIDER: S-EPMC12633387 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature