Abstract PR01: 3D enhancer clusters in the response to Wnt-driven colorectal cancer

Super-enhancers are clusters of enhancers that drive expression of genes key to development and cancer. We recently showed that super-enhancers and their target genes occur within DNA loops bounded by CTCF proteins. These chromosome structures constrain the activities of enhancers to genes that occur within the same loop, and were thus called insulated neighborhoods. Recent studies have shown that signaling pathways converge on super-enhancers, but the effect of signaling-mediated gene activation has yet to be investigated in the context of insulated neighborhood structure and function. We used a model of Wnt-pathway activation in colon cancer to investigate Wnt-mediated activation of target genes within insulated neighborhoods. When the Wnt-pathway was activated through genetic deletion of the tumor suppressor Apc in intestinal organoids, all enhancers within insulated neighborhoods that contained Tcf4 binding sites were activated, including enhancers that were not considered to contribute to super-enhancers. Thus, Wnt-stimulation co-activated multiple enhancers that are not in linear proximity, yet cluster in 3D space within insulated neighborhoods. We conclude that insulated neighborhoods allow the formation of 3D enhancer clusters whose constituents can operate concertedly, and thus expand the definition of super-enhancers to incorporate 3D chromatin organization.This abstract is also presented as Poster A15.Citation Format: Jurian Schuijers, Daniel S. Day, Violaine Saint...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Epigenetics: Oral Presentations - Proffered Abstracts Source Type: research