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Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework

Martin, Patrick CN and Zabet, Nicolae Radu (2020) 'Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework.' Computational and Structural Biotechnology Journal, 18. pp. 3590-3605. ISSN 2001-0370

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Transcription Factors (TFs) bind to DNA and control activity of target genes. Here, we present ChIPanalyser, a user-friendly, versatile and powerful R/Bioconductor package predicting and modelling the binding of TFs to DNA. ChIPanalyser performs similarly to state-of-the-art tools, but is an explainable model and provides biological insights into binding mechanisms of TFs. We focused on investigating the binding mechanisms of three TFs that are known architectural proteins CTCF, BEAF-32 and su(Hw) in three Drosophila cell lines (BG3, Kc167 and S2). While CTCF preferentially binds only to a subset of high affinity sites located mainly in open chromatin, BEAF-32 binds to most of its high affinity binding sites available in open chromatin. In contrast, su(Hw) binds to both open chromatin and also partially closed chromatin. Most importantly, differences in TF binding profiles between cell lines for these TFs are mainly driven by differences in DNA accessibility and not by differences in TF concentrations between cell lines. Finally, we investigated binding of Hox TFs in Drosophila and found that Ubx binds only in open chromatin, while Abd-B and Dfd are capable to bind in both open and partially closed chromatin. Overall, our results show that TFs display different binding mechanisms and that our model is able to recapitulate their specific binding behaviour.

Item Type: Article
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 06 Nov 2020 10:58
Last Modified: 18 Aug 2022 10:39

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