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 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.
|Year of Publication
2012 Sep 14
|PubMed Central ID
U54 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