TY - JOUR
T1 - A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
AU - Garber, Manuel
AU - Yosef, Nir
AU - Goren, Alon
AU - Raychowdhury, Raktima
AU - Thielke, Anne
AU - Guttman, Mitchell
AU - Robinson, James
AU - Minie, Brian
AU - Chevrier, Nicolas
AU - Itzhaki, Zohar
AU - Blecher-Gonen, Ronnie
AU - Bornstein, Chamutal
AU - Amann-Zalcenstein, Daniela
AU - Weiner, Assaf
AU - Friedrich, Dennis
AU - Meldrim, James
AU - Ram, Oren
AU - Cheng, Christine
AU - Gnirke, Andreas
AU - Fisher, Sheila
AU - Friedman, Nir
AU - Wong, Bang
AU - Bernstein, Bradley E.
AU - Nusbaum, Chad
AU - Hacohen, Nir
AU - Regev, Aviv
AU - Amit, Ido
PY - 2012/9/14
Y1 - 2012/9/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2012.07.030
DO - 10.1016/j.molcel.2012.07.030
M3 - Article
C2 - 22940246
AN - SCOPUS:84866303839
SN - 1097-2765
VL - 47
SP - 810
EP - 822
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -