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Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets

Gene expression governs cell fate, and is regulated via a complex interplay of transcription factors and molecules that change chromatin structure. Advances in sequencing-based assays have enabled investigation of these processes genome-wide, leading to large datasets that combine information on the...

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Autores principales: Vijayabaskar, M. S., Goode, Debbie K., Obier, Nadine, Lichtinger, Monika, Emmett, Amber M. L., Abidin, Fatin N. Zainul, Shar, Nisar, Hannah, Rebecca, Assi, Salam A., Lie-A-Ling, Michael, Gottgens, Berthold, Lacaud, Georges, Kouskoff, Valerie, Bonifer, Constanze, Westhead, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855567/
https://www.ncbi.nlm.nih.gov/pubmed/31682597
http://dx.doi.org/10.1371/journal.pcbi.1007337
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author Vijayabaskar, M. S.
Goode, Debbie K.
Obier, Nadine
Lichtinger, Monika
Emmett, Amber M. L.
Abidin, Fatin N. Zainul
Shar, Nisar
Hannah, Rebecca
Assi, Salam A.
Lie-A-Ling, Michael
Gottgens, Berthold
Lacaud, Georges
Kouskoff, Valerie
Bonifer, Constanze
Westhead, David R.
author_facet Vijayabaskar, M. S.
Goode, Debbie K.
Obier, Nadine
Lichtinger, Monika
Emmett, Amber M. L.
Abidin, Fatin N. Zainul
Shar, Nisar
Hannah, Rebecca
Assi, Salam A.
Lie-A-Ling, Michael
Gottgens, Berthold
Lacaud, Georges
Kouskoff, Valerie
Bonifer, Constanze
Westhead, David R.
author_sort Vijayabaskar, M. S.
collection PubMed
description Gene expression governs cell fate, and is regulated via a complex interplay of transcription factors and molecules that change chromatin structure. Advances in sequencing-based assays have enabled investigation of these processes genome-wide, leading to large datasets that combine information on the dynamics of gene expression, transcription factor binding and chromatin structure as cells differentiate. While numerous studies focus on the effects of these features on broader gene regulation, less work has been done on the mechanisms of gene-specific transcriptional control. In this study, we have focussed on the latter by integrating gene expression data for the in vitro differentiation of murine ES cells to macrophages and cardiomyocytes, with dynamic data on chromatin structure, epigenetics and transcription factor binding. Combining a novel strategy to identify communities of related control elements with a penalized regression approach, we developed individual models to identify the potential control elements predictive of the expression of each gene. Our models were compared to an existing method and evaluated using the existing literature and new experimental data from embryonic stem cell differentiation reporter assays. Our method is able to identify transcriptional control elements in a gene specific manner that reflect known regulatory relationships and to generate useful hypotheses for further testing.
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spelling pubmed-68555672019-12-06 Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets Vijayabaskar, M. S. Goode, Debbie K. Obier, Nadine Lichtinger, Monika Emmett, Amber M. L. Abidin, Fatin N. Zainul Shar, Nisar Hannah, Rebecca Assi, Salam A. Lie-A-Ling, Michael Gottgens, Berthold Lacaud, Georges Kouskoff, Valerie Bonifer, Constanze Westhead, David R. PLoS Comput Biol Research Article Gene expression governs cell fate, and is regulated via a complex interplay of transcription factors and molecules that change chromatin structure. Advances in sequencing-based assays have enabled investigation of these processes genome-wide, leading to large datasets that combine information on the dynamics of gene expression, transcription factor binding and chromatin structure as cells differentiate. While numerous studies focus on the effects of these features on broader gene regulation, less work has been done on the mechanisms of gene-specific transcriptional control. In this study, we have focussed on the latter by integrating gene expression data for the in vitro differentiation of murine ES cells to macrophages and cardiomyocytes, with dynamic data on chromatin structure, epigenetics and transcription factor binding. Combining a novel strategy to identify communities of related control elements with a penalized regression approach, we developed individual models to identify the potential control elements predictive of the expression of each gene. Our models were compared to an existing method and evaluated using the existing literature and new experimental data from embryonic stem cell differentiation reporter assays. Our method is able to identify transcriptional control elements in a gene specific manner that reflect known regulatory relationships and to generate useful hypotheses for further testing. Public Library of Science 2019-11-04 /pmc/articles/PMC6855567/ /pubmed/31682597 http://dx.doi.org/10.1371/journal.pcbi.1007337 Text en © 2019 Vijayabaskar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vijayabaskar, M. S.
Goode, Debbie K.
Obier, Nadine
Lichtinger, Monika
Emmett, Amber M. L.
Abidin, Fatin N. Zainul
Shar, Nisar
Hannah, Rebecca
Assi, Salam A.
Lie-A-Ling, Michael
Gottgens, Berthold
Lacaud, Georges
Kouskoff, Valerie
Bonifer, Constanze
Westhead, David R.
Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title_full Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title_fullStr Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title_full_unstemmed Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title_short Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets
title_sort identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: an integrative approach using high-throughput datasets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855567/
https://www.ncbi.nlm.nih.gov/pubmed/31682597
http://dx.doi.org/10.1371/journal.pcbi.1007337
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