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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037020304736 |
| _version_ | 1818573674313154560 |
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| author | Patrick C.N. Martin Nicolae Radu Zabet |
| author_facet | Patrick C.N. Martin Nicolae Radu Zabet |
| author_sort | Patrick C.N. Martin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-15T00:14:49Z |
| format | Article |
| id | doaj.art-ac19e7889479437fbac526f7ebf36160 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-15T00:14:49Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-ac19e7889479437fbac526f7ebf361602022-12-21T22:42:28ZengElsevierComputational and Structural Biotechnology Journal2001-03702020-01-011835903605Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics frameworkPatrick C.N. Martin0Nicolae Radu Zabet1School of Life Sciences, University of Essex, Colchester CO4 3SQ, UK; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, DenmarkSchool of Life Sciences, University of Essex, Colchester CO4 3SQ, UK; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK; Corresponding author at: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.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.http://www.sciencedirect.com/science/article/pii/S2001037020304736 |
| spellingShingle | Patrick C.N. Martin Nicolae Radu Zabet Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework Computational and Structural Biotechnology Journal |
| title | Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework |
| title_full | Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework |
| title_fullStr | Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework |
| title_full_unstemmed | Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework |
| title_short | Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework |
| title_sort | dissecting the binding mechanisms of transcription factors to dna using a statistical thermodynamics framework |
| url | http://www.sciencedirect.com/science/article/pii/S2001037020304736 |
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