A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals

Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin ImmunoPrecipitation (HT-ChIP) method to systematically map pr...

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Main Authors: Garber, Manuel, Yosef, Nir, Goren, Alon, Raychowdhury, Raktima, Thielke, Anne, Guttman, Mitchell, Robinson, James, Minie, Brian, Chevrier, Nicolas, Itzhaki, Zohar, Blecher-Gonen, Ronnie, Bornstein, Chamutal, Amann-Zalcenstein, Daniela, Weiner, Assaf, Friedrich, Dennis C., Meldrim, James C., Ram, Oren, Cheng, Christine S., Gnirke, Andreas, Fisher, Sheila, Friedman, Nir, Wong, Bang, Bernstein, Bradley E., Nusbaum, Chad, Hacohen, Nir, Regev, Aviv, Amit, Ido
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2014
Online Access:http://hdl.handle.net/1721.1/91898
https://orcid.org/0000-0002-9512-9127
https://orcid.org/0000-0001-8567-2049
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author Garber, Manuel
Yosef, Nir
Goren, Alon
Raychowdhury, Raktima
Thielke, Anne
Guttman, Mitchell
Robinson, James
Minie, Brian
Chevrier, Nicolas
Itzhaki, Zohar
Blecher-Gonen, Ronnie
Bornstein, Chamutal
Amann-Zalcenstein, Daniela
Weiner, Assaf
Friedrich, Dennis C.
Meldrim, James C.
Ram, Oren
Cheng, Christine S.
Gnirke, Andreas
Fisher, Sheila
Friedman, Nir
Wong, Bang
Bernstein, Bradley E.
Nusbaum, Chad
Hacohen, Nir
Regev, Aviv
Amit, Ido
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Garber, Manuel
Yosef, Nir
Goren, Alon
Raychowdhury, Raktima
Thielke, Anne
Guttman, Mitchell
Robinson, James
Minie, Brian
Chevrier, Nicolas
Itzhaki, Zohar
Blecher-Gonen, Ronnie
Bornstein, Chamutal
Amann-Zalcenstein, Daniela
Weiner, Assaf
Friedrich, Dennis C.
Meldrim, James C.
Ram, Oren
Cheng, Christine S.
Gnirke, Andreas
Fisher, Sheila
Friedman, Nir
Wong, Bang
Bernstein, Bradley E.
Nusbaum, Chad
Hacohen, Nir
Regev, Aviv
Amit, Ido
author_sort Garber, Manuel
collection MIT
description Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin ImmunoPrecipitation (HT-ChIP) method to systematically map protein-DNA interactions. HT-ChIP was applied to define the dynamics of DNA binding by 25 TFs and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 TF-DNA interactions we find that TFs vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby TF networks are hierarchically organized into cell differentiation factors, factors that bind targets prior to stimulus to prime them for induction, and factors that regulate specific gene programs. Overlaying HT-ChIP data on gene-expression dynamics shows that many TF-DNA interactions are established prior to the stimuli, predominantly at immediate-early genes, and identified specific TF ensembles that coordinately regulate gene-induction.
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spelling mit-1721.1/918982022-09-30T01:52:35Z A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals Garber, Manuel Yosef, Nir Goren, Alon Raychowdhury, Raktima Thielke, Anne Guttman, Mitchell Robinson, James Minie, Brian Chevrier, Nicolas Itzhaki, Zohar Blecher-Gonen, Ronnie Bornstein, Chamutal Amann-Zalcenstein, Daniela Weiner, Assaf Friedrich, Dennis C. Meldrim, James C. Ram, Oren Cheng, Christine S. Gnirke, Andreas Fisher, Sheila Friedman, Nir Wong, Bang Bernstein, Bradley E. Nusbaum, Chad Hacohen, Nir Regev, Aviv Amit, Ido Massachusetts Institute of Technology. Department of Biology Sloan School of Management Fisher, Sheila Regev, Aviv Guttman, Mitchell Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin ImmunoPrecipitation (HT-ChIP) method to systematically map protein-DNA interactions. HT-ChIP was applied to define the dynamics of DNA binding by 25 TFs and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 TF-DNA interactions we find that TFs vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby TF networks are hierarchically organized into cell differentiation factors, factors that bind targets prior to stimulus to prime them for induction, and factors that regulate specific gene programs. Overlaying HT-ChIP data on gene-expression dynamics shows that many TF-DNA interactions are established prior to the stimuli, predominantly at immediate-early genes, and identified specific TF ensembles that coordinately regulate gene-induction. Broad Institute of MIT and Harvard United States. Defense Advanced Research Projects Agency (D12AP00004) Howard Hughes Medical Institute National Human Genome Research Institute (U.S.) (Grant 1P01HG005062-01) National Institutes of Health (U.S.). Pioneer Award (DP1-OD003958-01) Burroughs Wellcome Fund (Career Award at the Scientific Interface) National Human Genome Research Institute (U.S.) Center of Excellence in Genome Science (1P50HG006193) United States-Israel Binational Science Foundation 2014-11-24T22:01:01Z 2014-11-24T22:01:01Z 2012-08 2012-07 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/91898 Garber, Manuel, Nir Yosef, Alon Goren, Raktima Raychowdhury, Anne Thielke, Mitchell Guttman, James Robinson, et al. “A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals.” Molecular Cell 47, no. 5 (September 2012): 810–822. © 2012 Elsevier Inc. https://orcid.org/0000-0002-9512-9127 https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.molcel.2012.07.030 Molecular Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle Garber, Manuel
Yosef, Nir
Goren, Alon
Raychowdhury, Raktima
Thielke, Anne
Guttman, Mitchell
Robinson, James
Minie, Brian
Chevrier, Nicolas
Itzhaki, Zohar
Blecher-Gonen, Ronnie
Bornstein, Chamutal
Amann-Zalcenstein, Daniela
Weiner, Assaf
Friedrich, Dennis C.
Meldrim, James C.
Ram, Oren
Cheng, Christine S.
Gnirke, Andreas
Fisher, Sheila
Friedman, Nir
Wong, Bang
Bernstein, Bradley E.
Nusbaum, Chad
Hacohen, Nir
Regev, Aviv
Amit, Ido
A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title_full A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title_fullStr A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title_full_unstemmed A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title_short A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
title_sort high throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals
url http://hdl.handle.net/1721.1/91898
https://orcid.org/0000-0002-9512-9127
https://orcid.org/0000-0001-8567-2049
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