Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility

David Lamparter; Daniel Marbach; Rico Rueedi; Sven Bergmann; Zoltán Kutalik

doi:10.1371/journal.pcbi.1005311

Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility

PLoS Comput Biol. 2017 Jan 24;13(1):e1005311. doi: 10.1371/journal.pcbi.1005311. eCollection 2017 Jan.

Authors

David Lamparter^{1

2}, Daniel Marbach^{1

2}, Rico Rueedi^{1

2}, Sven Bergmann^{1

2

3}, Zoltán Kutalik^{2

4}

Affiliations

¹ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
² Swiss institute of Bioinformatics, Lausanne, Switzerland.
³ Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
⁴ Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.

Abstract

To better understand genome regulation, it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance. Here we present a data-driven approach to systematically characterise transcription factors that are relevant for this process. Our method uses a linear mixed modelling approach to combine datasets of transcription factor binding motif enrichments in open chromatin and gene expression across the same set of cell lines. Applying this approach to the ENCODE dataset, we confirm already known and imply numerous novel transcription factors that play a role in the establishment or maintenance of open chromatin. In particular, our approach rediscovers many factors that have been annotated as pioneer factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites / genetics
Cell Line
Chromatin / chemistry*
Chromatin / genetics*
Chromatin / metabolism
Chromatin Immunoprecipitation
Computational Biology
Genome-Wide Association Study*
Humans
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

Chromatin
Transcription Factors

Grants and funding

This work was supported by the Leenards Foundation (http://www.leenaards.ch) [to ZK] the Swiss Institute of Bioinformatics (http://www.isb-sib.ch/) [to SB, to ZK], the Swiss National Science Foundation [31003A-143914 to ZK, FN 310030_152724 / 1 to SB] and SystemsX.ch (http://www.systemsx.ch/) [51RTP0_151019 to ZK, via SysGenetiX to SB]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.