title: A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals.
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.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. manuel.garber@umassmed.edu
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.forename: Alon
authors.initials: A
authors.lastname: Goren
authors.forename: Raktima
authors.initials: R
authors.lastname: Raychowdhury
authors.forename: Anne
authors.initials: A
authors.lastname: Thielke
authors.forename: Mitchell
authors.initials: M
authors.lastname: Guttman
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Brian
authors.initials: B
authors.lastname: Minie
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevrier
authors.forename: Zohar
authors.initials: Z
authors.lastname: Itzhaki
authors.forename: Ronnie
authors.initials: R
authors.lastname: Blecher-Gonen
authors.forename: Chamutal
authors.initials: C
authors.lastname: Bornstein
authors.forename: Daniela
authors.initials: D
authors.lastname: Amann-Zalcenstein
authors.forename: Assaf
authors.initials: A
authors.lastname: Weiner
authors.forename: Dennis
authors.initials: D
authors.lastname: Friedrich
authors.forename: James
authors.initials: J
authors.lastname: Meldrim
authors.forename: Oren
authors.initials: O
authors.lastname: Ram
authors.forename: Christine
authors.initials: C
authors.lastname: Cheng
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: Sheila
authors.initials: S
authors.lastname: Fisher
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.forename: Bang
authors.initials: B
authors.lastname: Wong
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D057166:High-Throughput Screening Assays; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D004247:DNA