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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
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 |
_version_ | 1826188633628999680 |
---|---|
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. |
first_indexed | 2024-09-23T08:02:22Z |
format | Article |
id | mit-1721.1/91898 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T08:02:22Z |
publishDate | 2014 |
publisher | Elsevier |
record_format | dspace |
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 |
work_keys_str_mv | AT garbermanuel ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT yosefnir ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT gorenalon ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT raychowdhuryraktima ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT thielkeanne ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT guttmanmitchell ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT robinsonjames ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT miniebrian ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT chevriernicolas ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT itzhakizohar ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT blechergonenronnie ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT bornsteinchamutal ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT amannzalcensteindaniela ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT weinerassaf ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT friedrichdennisc ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT meldrimjamesc ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT ramoren ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT chengchristines ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT gnirkeandreas ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT fishersheila ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT friedmannir ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT wongbang ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT bernsteinbradleye ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT nusbaumchad ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT hacohennir ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT regevaviv ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT amitido ahighthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT garbermanuel highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT yosefnir highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT gorenalon highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT raychowdhuryraktima highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT thielkeanne highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT guttmanmitchell highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT robinsonjames highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT miniebrian highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT chevriernicolas highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT itzhakizohar highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT blechergonenronnie highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT bornsteinchamutal highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT amannzalcensteindaniela highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT weinerassaf highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT friedrichdennisc highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT meldrimjamesc highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT ramoren highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT chengchristines highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT gnirkeandreas highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT fishersheila highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT friedmannir highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT wongbang highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT bernsteinbradleye highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT nusbaumchad highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT hacohennir highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT regevaviv highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals AT amitido highthroughputchromatinimmunoprecipitationapproachrevealsprinciplesofdynamicgeneregulationinmammals |