Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models
Transcription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families...
| Main Authors: | , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/115256 https://orcid.org/0000-0002-3583-3112 |
| _version_ | 1811086625003798528 |
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| author | Yang, Lin Orenstein, Yaron Jolma, Arttu Yin, Yimeng Taipale, Jussi Shamir, Ron Rohs, Remo |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Yang, Lin Orenstein, Yaron Jolma, Arttu Yin, Yimeng Taipale, Jussi Shamir, Ron Rohs, Remo |
| author_sort | Yang, Lin |
| collection | MIT |
| description | Transcription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families, or whether this mechanism is used extensively by most TF families. We resequenced data from previously published HT-SELEX experiments, the most extensive mammalian TF–DNA binding data available to date. Using these data, we demonstrated the contributions of DNA shape readout across diverse TF families and its importance in core motif-flanking regions. Statistical machine-learning models combined with feature-selection techniques helped to reveal the nucleotide position-dependent DNA shape readout in TF-binding sites and the TF family-specific position dependence. Based on these results, we proposed novel DNA shape logos to visualize the DNA shape preferences of TFs. Overall, this work suggests a way of obtaining mechanistic insights into TF–DNA binding without relying on experimentally solved all-atom structures. |
| first_indexed | 2024-09-23T13:29:13Z |
| format | Article |
| id | mit-1721.1/115256 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:29:13Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1152562022-10-01T15:34:25Z Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models Yang, Lin Orenstein, Yaron Jolma, Arttu Yin, Yimeng Taipale, Jussi Shamir, Ron Rohs, Remo Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Orenstein, Yaron Transcription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families, or whether this mechanism is used extensively by most TF families. We resequenced data from previously published HT-SELEX experiments, the most extensive mammalian TF–DNA binding data available to date. Using these data, we demonstrated the contributions of DNA shape readout across diverse TF families and its importance in core motif-flanking regions. Statistical machine-learning models combined with feature-selection techniques helped to reveal the nucleotide position-dependent DNA shape readout in TF-binding sites and the TF family-specific position dependence. Based on these results, we proposed novel DNA shape logos to visualize the DNA shape preferences of TFs. Overall, this work suggests a way of obtaining mechanistic insights into TF–DNA binding without relying on experimentally solved all-atom structures. 2018-05-09T15:48:50Z 2018-05-09T15:48:50Z 2017-02 2017-01 2018-05-09T14:38:16Z Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/115256 Yang, Lin et al. “Transcription Factor Family‐specific DNA Shape Readout Revealed by Quantitative Specificity Models.” Molecular Systems Biology 13, 2 (February 2017): 910 © 2017 The Authors https://orcid.org/0000-0002-3583-3112 http://dx.doi.org/10.15252/msb.20167238 Molecular Systems Biology Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group EMBRO Press |
| spellingShingle | Yang, Lin Orenstein, Yaron Jolma, Arttu Yin, Yimeng Taipale, Jussi Shamir, Ron Rohs, Remo Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title | Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title_full | Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title_fullStr | Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title_full_unstemmed | Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title_short | Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models |
| title_sort | transcription factor family specific dna shape readout revealed by quantitative specificity models |
| url | http://hdl.handle.net/1721.1/115256 https://orcid.org/0000-0002-3583-3112 |
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