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

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 FisherNir Friedman, Bang Wong, Bradley E. Bernstein, Chad Nusbaum, Nir Hacohen, Aviv Regev, Ido Amit

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)810-822
Number of pages13
JournalMolecular Cell
Volume47
Issue number5
DOIs
Publication statusPublished - Sep 14 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Garber, M., Yosef, N., Goren, A., Raychowdhury, R., Thielke, A., Guttman, M., ... Amit, I. (2012). A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals. Molecular Cell, 47(5), 810-822. https://doi.org/10.1016/j.molcel.2012.07.030