Garber Lab Publications

Title

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

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Garber Lab

Publication Date

2012-09-14

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Bioinformatics | Cell Biology | Computational Biology | Genetic Phenomena | Genomics | Molecular Biology

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.

DOI of Published Version

10.1016/j.molcel.2012.07.030

Source

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

Journal/Book/Conference Title

Molecular cell

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

22940246

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