RT Journal Article
SR Electronic
T1 Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 666446
DO 10.1101/666446
A1 Martin, Patrick C.N.
A1 Zabet, Nicolae Radu
YR 2019
UL http://biorxiv.org/content/early/2019/06/11/666446.abstract
AB At the heart of gene regulation are Transcription Factors (TF), proteins which bind to DNA in a sequence specific manner and drive the activation or repression of genes. Here, we present a statistical thermodynamics framework (ChIPanalyser) which models and predicts binding 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 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 regions displaying intermediate levels of accessibility. 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 prefers open chromatin, while Abd-B and Dfd are capable to bind in 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.