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

David Lamparter, Daniel Marbach, Rico Rueedi, Sven Bergmann and Zoltán Kutalik

PLOS Computational Biology, 2017, vol. 13, issue 1, 1-19

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.Author Summary: Transcription factor binding occurs mainly in regions of open chromatin. For many transcription factors, it is unclear whether binding is the cause or the consequence of open chromatin. Here, we used datasets on open chromatin and gene expression provided by the ENCODE project to predict which transcription factors drive transitions between open and closed states. A signature of such a factor is that its expression values are correlated to chromatin accessibility at its motif across the same set of cell lines. Our method assesses this correlation while accounting for the fact that some tested cell lines are more related than others. We find many transcription factors showing evidence of driving transitions and a high proportion of these transcription factors are known pioneer factors, i.e., they play a role in opening up closed chromatin.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1005311

DOI: 10.1371/journal.pcbi.1005311

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