Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization
Date
2024
Authors
Advisors
Journal Title
Journal ISSN
Volume Title
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 spatial separation improves the computational prediction of validated enhancers. Thus, we propose a new model of enhancer organization incorporating spatial separation of essential functional and structural components.
Type
Department
Description
Provenance
Citation
Permalink
Citation
Cerda-Smith, Christian Gonzalo (2024). Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/30786.
Collections
Dukes student scholarship is made available to the public using a Creative Commons Attribution / Non-commercial / No derivative (CC-BY-NC-ND) license.