A genome-wide interactome of DNA-associated proteins in the human liver
- Ryne C. Ramaker1,2,3,
- Daniel Savic1,3,4,
- Andrew A. Hardigan1,2,
- Kimberly Newberry1,
- Gregory M. Cooper1,
- Richard M. Myers1 and
- Sara J. Cooper1
- 1HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA;
- 2Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
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↵3 These authors contributed equally to this work.
Abstract
Large-scale efforts like the ENCODE Project have made tremendous progress in cataloging the genomic binding patterns of DNA-associated proteins (DAPs), such as transcription factors (TFs). However, most chromatin immunoprecipitation-sequencing (ChIP-seq) analyses have focused on a few immortalized cell lines whose activities and physiology differ in important ways from endogenous cells and tissues. Consequently, binding data from primary human tissue are essential to improving our understanding of in vivo gene regulation. Here, we identify and analyze more than 440,000 binding sites using ChIP-seq data for 20 DAPs in two human liver tissue samples. We integrated binding data with transcriptome and phased WGS data to investigate allelic DAP interactions and the impact of heterozygous sequence variation on the expression of neighboring genes. Our tissue-based data set exhibits binding patterns more consistent with liver biology than cell lines, and we describe uses of these data to better prioritize impactful noncoding variation. Collectively, our rich data set offers novel insights into genome function in human liver tissue and provides a valuable resource for assessing disease-related disruptions.
Footnotes
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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.222083.117.
- Received February 23, 2017.
- Accepted August 22, 2017.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
