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

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 explain...

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Bibliographic Details
Published inbioRxiv
Main Authors Martin, Patrick C N, Nicolae Radu Zabet
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 22.08.2020
Subjects
Affinity
Binding sites
Cell lines
Chromatin
Deoxyribonucleic acid
DNA
Drosophila
Gene regulation
Gene silencing
Insects
Nucleotide sequence
Statistical analysis
Statistics
Thermodynamics
Transcription activation
Transcription factors
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Summary: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 this diverse repertoire of mechanisms. Competing Interest Statement The authors have declared no competing interest. Footnotes * we introduced a comparison with other tools, and new validation strategies (e.g., chromosome withhold)
DOI:10.1101/666446