Vangala, PranithaMurphy, RachelQuinodoz, Sofia A.Gellatly, Kyle J.McDonel, Patrick E.Guttman, MitchellGarber, Manuel2022-08-232022-08-232020-10-152020-11-16<p>Vangala P, Murphy R, Quinodoz SA, Gellatly K, McDonel P, Guttman M, Garber M. High-Resolution Mapping of Multiway Enhancer-Promoter Interactions Regulating Pathogen Detection. Mol Cell. 2020 Oct 15;80(2):359-373.e8. doi: 10.1016/j.molcel.2020.09.005. Epub 2020 Sep 28. PMID: 32991830; PMCID: PMC7572724. <a href="https://doi.org/10.1016/j.molcel.2020.09.005">Link to article on publisher's site</a></p>1097-2765 (Linking)10.1016/j.molcel.2020.09.00532991830https://hdl.handle.net/20.500.14038/29614Eukaryotic gene expression regulation involves thousands of distal regulatory elements. Understanding the quantitative contribution of individual enhancers to gene expression is critical for assessing the role of disease-associated genetic risk variants. Yet, we lack the ability to accurately link genes with their distal regulatory elements. To address this, we used 3D enhancer-promoter (E-P) associations identified using split-pool recognition of interactions by tag extension (SPRITE) to build a predictive model of gene expression. Our model dramatically outperforms models using genomic proximity and can be used to determine the quantitative impact of enhancer loss on gene expression in different genetic backgrounds. We show that genes that form stable E-P hubs have less cell-to-cell variability in gene expression. Finally, we identified transcription factors that regulate stimulation-dependent E-P interactions. Together, our results provide a framework for understanding quantitative contributions of E-P interactions and associated genetic variants to gene expression.en-USchromosome conformationcis-regulatory elementsdendritic cellsenhancersgenetic variationinnate immunitymachine learningmultiway promoter interactionssingle cellsingle moleculeAmino Acids, Peptides, and ProteinsBiochemistry, Biophysics, and Structural BiologyBioinformaticsGenetics and GenomicsMolecular BiologyJournal Articlehttps://escholarship.umassmed.edu/faculty_pubs/183120206051faculty_pubs/1831