Inferring chromatin-bound protein complexes from genome-wide binding assays
- 1HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, Cornell University, New York, New York 10021, USA;
- 2Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, New York, New York 10021, USA
Abstract
Genome-wide binding assays can determine where individual transcription factors bind in the genome. However, these factors rarely bind chromatin alone, but instead frequently bind to cis-regulatory elements (CREs) together with other factors thus forming protein complexes. Currently there are no integrative analytical approaches that can predict which complexes are formed on chromatin. Here, we describe a computational methodology to systematically capture protein complexes and infer their impact on gene expression. We applied our method to three human cell types, identified thousands of CREs, inferred known and undescribed complexes recruited to these CREs, and determined the role of the complexes as activators or repressors. Importantly, we found that the predicted complexes have a higher number of physical interactions between their members than expected by chance. Our work provides a mechanism for developing hypotheses about gene regulation via binding partners, and deciphering the interplay between combinatorial binding and gene expression.
Footnotes
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↵3 Corresponding author
E-mail ole2001{at}med.cornell.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.149419.112.
Freely available online through the Genome Research Open Access option.
- Received September 18, 2012.
- Accepted April 2, 2013.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
