Transcription Factor Binding Affinities and DNA Shape Readout
Summary: An essential event in gene regulation is the binding of a transcription factor (TF) to its target DNA. Models considering the interactions between the TF and the DNA geometry proved to be successful approaches to describe this binding event, while conserving data interpretability. However,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220308865 |
| _version_ | 1818454542570749952 |
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| author | Max Schnepf Marc von Reutern Claudia Ludwig Christophe Jung Ulrike Gaul |
| author_facet | Max Schnepf Marc von Reutern Claudia Ludwig Christophe Jung Ulrike Gaul |
| author_sort | Max Schnepf |
| collection | DOAJ |
| description | Summary: An essential event in gene regulation is the binding of a transcription factor (TF) to its target DNA. Models considering the interactions between the TF and the DNA geometry proved to be successful approaches to describe this binding event, while conserving data interpretability. However, a direct characterization of the DNA shape contribution to binding is still missing due to the lack of accurate and large-scale binding affinity data. Here, we use a binding assay we recently established to measure with high sensitivity the binding specificities of 13 Drosophila TFs, including dinucleotide dependencies to capture non-independent amino acid-base interactions. Correlating the binding affinities with all DNA shape features, we find that shape readout is widely used by these factors. A shape readout/TF-DNA complex structure analysis validates our approach while providing biological insights such as positively charged or highly polar amino acids often contact nucleotides that exhibit strong shape readout. |
| first_indexed | 2024-12-14T21:56:32Z |
| format | Article |
| id | doaj.art-1b38da966e3646fabf2d9bbd8f579b0c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T21:56:32Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1b38da966e3646fabf2d9bbd8f579b0c2022-12-21T22:46:07ZengElsevieriScience2589-00422020-11-012311101694Transcription Factor Binding Affinities and DNA Shape ReadoutMax Schnepf0Marc von Reutern1Claudia Ludwig2Christophe Jung3Ulrike Gaul4Gene Center and Department of Biochemistry, Center for Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, GermanyGene Center and Department of Biochemistry, Center for Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, GermanyGene Center and Department of Biochemistry, Center for Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, GermanyGene Center and Department of Biochemistry, Center for Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, Germany; Corresponding authorGene Center and Department of Biochemistry, Center for Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, GermanySummary: An essential event in gene regulation is the binding of a transcription factor (TF) to its target DNA. Models considering the interactions between the TF and the DNA geometry proved to be successful approaches to describe this binding event, while conserving data interpretability. However, a direct characterization of the DNA shape contribution to binding is still missing due to the lack of accurate and large-scale binding affinity data. Here, we use a binding assay we recently established to measure with high sensitivity the binding specificities of 13 Drosophila TFs, including dinucleotide dependencies to capture non-independent amino acid-base interactions. Correlating the binding affinities with all DNA shape features, we find that shape readout is widely used by these factors. A shape readout/TF-DNA complex structure analysis validates our approach while providing biological insights such as positively charged or highly polar amino acids often contact nucleotides that exhibit strong shape readout.http://www.sciencedirect.com/science/article/pii/S2589004220308865BiomoleculesMolecular BiologyMolecular Mechanism of Gene Regulation |
| spellingShingle | Max Schnepf Marc von Reutern Claudia Ludwig Christophe Jung Ulrike Gaul Transcription Factor Binding Affinities and DNA Shape Readout iScience Biomolecules Molecular Biology Molecular Mechanism of Gene Regulation |
| title | Transcription Factor Binding Affinities and DNA Shape Readout |
| title_full | Transcription Factor Binding Affinities and DNA Shape Readout |
| title_fullStr | Transcription Factor Binding Affinities and DNA Shape Readout |
| title_full_unstemmed | Transcription Factor Binding Affinities and DNA Shape Readout |
| title_short | Transcription Factor Binding Affinities and DNA Shape Readout |
| title_sort | transcription factor binding affinities and dna shape readout |
| topic | Biomolecules Molecular Biology Molecular Mechanism of Gene Regulation |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220308865 |
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