Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization.

ABSTRACT: Enhancers possess both structural elements mediating promoter looping and functional elements mediating gene expression. Traditional models of enhancer-mediated gene regulation imply genomic overlap or immediate adjacency of these elements. We test this model by combining densely-tiled CRISPRa screening with nucleosome-resolution Region Capture Micro-C topology analysis. Using this integrated approach, we comprehensively define the cis-regulatory landscape for the tumor suppressor PTEN, identifying and validating 10 distinct enhancers and defining their 3D spatial organization. Unexpectedly, we identify several long-range functional enhancers whose promoter proximity is facilitated by chromatin loop anchors several kilobases away, and demonstrate that accounting for this spat

SUBMITTER: Cerda-Smith CG 

PROVIDER: S-EPMC10541578 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature