High-Resolution Mapping of Multiway Enhancer-Promoter Interactions Regulating Pathogen Detection
Autor: | Manuel Garber, Kyle Gellatly, Mitchell Guttman, R. Murphy, Sofia A. Quinodoz, Pranitha Vangala, Patrick McDonel |
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Rok vydání: | 2020 |
Předmět: |
Pathogen detection
High resolution Computational biology Biology Models Biological Article 03 medical and health sciences 0302 clinical medicine Genetic variation Gene expression Animals Genetic risk Promoter Regions Genetic Enhancer Molecular Biology Transcription factor Gene 030304 developmental biology Stochastic Processes 0303 health sciences Bacteria Dendritic Cells Cell Biology Mice Inbred C57BL Enhancer Elements Genetic Gene Expression Regulation Linear Models Female 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Mol Cell |
ISSN: | 1097-2765 |
Popis: | Eukaryotic 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. |
Databáze: | OpenAIRE |
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