A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals
Program in Bioinformatics and Integrative Biology; Garber Lab
Amino Acids, Peptides, and Proteins | Bioinformatics | Cell Biology | Computational Biology | Genetic Phenomena | Genomics | Molecular Biology
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.
DOI of Published Version
Mol Cell. 2012 Sep 14;47(5):810-22. doi: 10.1016/j.molcel.2012.07.030. Epub 2012 Aug 30. Link to article on publisher's site
Garber, Manuel and Amit, Ido, "A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals" (2012). Garber Lab Publications. 5.