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

Garber, Manuel and Guttman, Mitchell (2012) A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals. Molecular Cell, 47 (5). pp. 810-822. ISSN 1097-2765. PMCID PMC3873101. doi:10.1016/j.molcel.2012.07.030.

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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.

Item Type:Article
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Guttman, Mitchell0000-0003-4748-9352
Additional Information:© 2012 Elsevier Inc. Received 12 April 2012, Revised 3 July 2012, Accepted 27 July 2012, Available online 30 August 2012 Published online: August 30, 2012 We thank Schraga Schwartz, Tommy Kaplan, Ami Citri, Kevin Struhl, Gioacchino Natoli, Richard Young, and John Rinn for valuable discussions and comments; Leslie Gaffney for artwork; Jim Bochicchio for project management; and the Broad Sequencing Platform. This project was supported by the Human Frontiers Science Program; Career Development Award; an ISF; Bikura Institutional Research Grant Program; ERC starting grant 309788 (I.A.); by the Broad Institute (M.G., N.Y., I.A., A.R.); and by DARPA D12AP00004 (M.G.). HHMI, NHGRI grant 1P01HG005062-01; an NIH PIONEER award DP1-OD003958-01; a Burroughs-Wellcome Fund Career Award at the Scientific Interface; and a Center for Excellence in Genome Science from the NHGRI 1P50HG006193 (A.R.); A.R. is a fellow of the Merkin Foundation for Stem Cell Research at the Broad Institute and by the New England Regional Center for Excellence/Biodefense and Emerging Infectious Disease U54 AI057159 (N.H.). EU FP7 Model-In (N.F.) and US-Israel Binational Science Foundation (N.F. and A.R.) Complete Sequencing data sets are available at the Gene Expression Omnibus (accession no. GSE36104).
Funding AgencyGrant Number
Human Frontiers Science ProgramUNSPECIFIED
Israel Science FoundationUNSPECIFIED
Bikura Institutional Research Grant ProgramUNSPECIFIED
European Research Council (ERC)309788
Broad Institute of MIT and HarvardUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)D12AP00004
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
NIHU54 AI057159
Richard Merkin Foundation for Stem Cell ResearchUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
National Human Genome Research InstituteUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC3873101
Record Number:CaltechAUTHORS:20161122-073136200
Persistent URL:
Official Citation:Manuel Garber, Nir Yosef, Alon Goren, Raktima Raychowdhury, Anne Thielke, Mitchell Guttman, James Robinson, Brian Minie, Nicolas Chevrier, Zohar Itzhaki, Ronnie Blecher-Gonen, Chamutal Bornstein, Daniela Amann-Zalcenstein, Assaf Weiner, Dennis Friedrich, James Meldrim, Oren Ram, Christine Cheng, Andreas Gnirke, Sheila Fisher, Nir Friedman, Bang Wong, Bradley E. Bernstein, Chad Nusbaum, Nir Hacohen, Aviv Regev, Ido Amit, A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals, Molecular Cell, Volume 47, Issue 5, 14 September 2012, Pages 810-822, ISSN 1097-2765, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72231
Deposited By: Ruth Sustaita
Deposited On:22 Nov 2016 18:32
Last Modified:11 Nov 2021 04:58

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