High Resolution Mapping of Enhancer-Promoter Interactions

RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spat...

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Main Authors: Reeder, Christopher, Closser, Michael, Poh, Huay Mei, Sandhu, Kuljeet, Wichterle, Hynek, Gifford, David K.
Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Format: Article
Language:en_US
Published: Public Library of Science 2015
Online Access:http://hdl.handle.net/1721.1/97115
https://orcid.org/0000-0003-1709-4034
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author Reeder, Christopher
Closser, Michael
Poh, Huay Mei
Sandhu, Kuljeet
Wichterle, Hynek
Gifford, David K.
author2 Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
author_facet Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Reeder, Christopher
Closser, Michael
Poh, Huay Mei
Sandhu, Kuljeet
Wichterle, Hynek
Gifford, David K.
author_sort Reeder, Christopher
collection MIT
description RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution that is insufficient to accurately identify individual enhancers. We introduce Germ, a computational method that estimates the likelihood that any two narrowly defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a blind deconvolution approach to simultaneously estimate the likelihood of RNA Polymerase II occupation as well as a model of the arrangement of read alignments relative to locations occupied by RNA Polymerase II. Both types of information are utilized to estimate the likelihood that RNA Polymerase II jointly occupies any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from embryonic stem cells to identify the genomic locations that are jointly occupied along with transcription start sites. We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool. We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.
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spelling mit-1721.1/971152022-09-27T15:21:20Z High Resolution Mapping of Enhancer-Promoter Interactions Reeder, Christopher Closser, Michael Poh, Huay Mei Sandhu, Kuljeet Wichterle, Hynek Gifford, David K. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Reeder, Christopher Gifford, David K. RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution that is insufficient to accurately identify individual enhancers. We introduce Germ, a computational method that estimates the likelihood that any two narrowly defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a blind deconvolution approach to simultaneously estimate the likelihood of RNA Polymerase II occupation as well as a model of the arrangement of read alignments relative to locations occupied by RNA Polymerase II. Both types of information are utilized to estimate the likelihood that RNA Polymerase II jointly occupies any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from embryonic stem cells to identify the genomic locations that are jointly occupied along with transcription start sites. We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool. We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression. National Institutes of Health (U.S.) (Grant 1U01HG007037) 2015-05-29T14:42:16Z 2015-05-29T14:42:16Z 2015-05 2014-11 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/97115 Reeder, Christopher, Michael Closser, Huay Mei Poh, Kuljeet Sandhu, Hynek Wichterle, and David Gifford. “High Resolution Mapping of Enhancer-Promoter Interactions.” Edited by Charalampos Babis Spilianakis. PLOS ONE 10, no. 5 (May 13, 2015): e0122420. https://orcid.org/0000-0003-1709-4034 en_US http://dx.doi.org/10.1371/journal.pone.0122420 PLOS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science
spellingShingle Reeder, Christopher
Closser, Michael
Poh, Huay Mei
Sandhu, Kuljeet
Wichterle, Hynek
Gifford, David K.
High Resolution Mapping of Enhancer-Promoter Interactions
title High Resolution Mapping of Enhancer-Promoter Interactions
title_full High Resolution Mapping of Enhancer-Promoter Interactions
title_fullStr High Resolution Mapping of Enhancer-Promoter Interactions
title_full_unstemmed High Resolution Mapping of Enhancer-Promoter Interactions
title_short High Resolution Mapping of Enhancer-Promoter Interactions
title_sort high resolution mapping of enhancer promoter interactions
url http://hdl.handle.net/1721.1/97115
https://orcid.org/0000-0003-1709-4034
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AT clossermichael highresolutionmappingofenhancerpromoterinteractions
AT pohhuaymei highresolutionmappingofenhancerpromoterinteractions
AT sandhukuljeet highresolutionmappingofenhancerpromoterinteractions
AT wichterlehynek highresolutionmappingofenhancerpromoterinteractions
AT gifforddavidk highresolutionmappingofenhancerpromoterinteractions