A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
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Garber-2012-A High-Throughput Ch.pdf
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Author(s)
Garber, Manuel
Yosef, Nir
Goren, Alon
Raychowdhury, Raktima
Thielke, Anne
Guttman, Mitchell
Robinson, James
Minie, Brian
Chevrier, Nicolas
Itzhaki, Zohar
Date Issued
August 2012
Journal
Molecular Cell
Publisher
Elsevier
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Sloan School of Management
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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.
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2012.07.030
