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Mol Cell DOI:10.1016/j.molcel.2012.07.030

A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals.

Publication TypeJournal Article
Year of Publication2012
AuthorsGarber, M, Yosef, N, Goren, A, Raychowdhury, R, Thielke, A, Guttman, M, Robinson, J, Minie, B, Chevrier, N, Itzhaki, Z, Blecher-Gonen, R, Bornstein, C, Amann-Zalcenstein, D, Weiner, A, Friedrich, D, Meldrim, J, Ram, O, Cheng, C, Gnirke, A, Fisher, S, Friedman, N, Wong, B, Bernstein, BE, Nusbaum, C, Hacohen, N, Regev, A, Amit, I
JournalMol Cell
Date Published2012 Sep 14
KeywordsAnimals, Chromatin Immunoprecipitation, Dendritic Cells, DNA, Gene Expression Regulation, High-Throughput Screening Assays, Mice, Transcription Factors

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.


Alternate JournalMol. Cell
PubMed ID22940246
PubMed Central IDPMC3873101
Grant ListU54 AI057159 / AI / NIAID NIH HHS / United States
F32 CA168253 / CA / NCI NIH HHS / United States
DP2 OD002230 / OD / NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
S10 RR026688 / RR / NCRR NIH HHS / United States