DNA-binding specificity changes in the evolution of forkhead transcription factors
The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and relate...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/88252 |
| _version_ | 1826207880626307072 |
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| author | Nakagawa, So Gisselbrecht, Stephen S. Rogers, Julia M. Hartl, Daniel L. Bulyk, Martha L. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Nakagawa, So Gisselbrecht, Stephen S. Rogers, Julia M. Hartl, Daniel L. Bulyk, Martha L. |
| author_sort | Nakagawa, So |
| collection | MIT |
| description | The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and related protists. We have used a combination of maximum-likelihood phylogenetic inference and independent, comprehensive functional assays of DNA-binding capacity to explore the evolution of DNA-binding specificity within the forkhead family. We present converging evidence that similar alternative sequence preferences have arisen repeatedly and independently in the course of forkhead evolution. The vast majority of DNA-binding specific city changes we observed are not explained by alterations in the known DNA-contacting amino acid residues conferring specificity for canonical forkhead binding sites. Intriguingly, we have found forkhead DBDs that retain the ability to bind very specifically to two completely distinct DNA sequence motifs.We propose an alternate specificity-determining mechanism whereby conformational rearrangements of the DBD broaden the spectrum of sequence motifs that a TF can recognize. DNA-binding bispecificity suggests a previously undescribed source of modularity and exibility in gene regulation and may play an important role in the evolution of transcriptional regulatory networks. |
| first_indexed | 2024-09-23T13:56:25Z |
| format | Article |
| id | mit-1721.1/88252 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:56:25Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/882522022-10-01T18:06:24Z DNA-binding specificity changes in the evolution of forkhead transcription factors Nakagawa, So Gisselbrecht, Stephen S. Rogers, Julia M. Hartl, Daniel L. Bulyk, Martha L. Harvard University--MIT Division of Health Sciences and Technology Gisselbrecht, Stephen S. The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and related protists. We have used a combination of maximum-likelihood phylogenetic inference and independent, comprehensive functional assays of DNA-binding capacity to explore the evolution of DNA-binding specificity within the forkhead family. We present converging evidence that similar alternative sequence preferences have arisen repeatedly and independently in the course of forkhead evolution. The vast majority of DNA-binding specific city changes we observed are not explained by alterations in the known DNA-contacting amino acid residues conferring specificity for canonical forkhead binding sites. Intriguingly, we have found forkhead DBDs that retain the ability to bind very specifically to two completely distinct DNA sequence motifs.We propose an alternate specificity-determining mechanism whereby conformational rearrangements of the DBD broaden the spectrum of sequence motifs that a TF can recognize. DNA-binding bispecificity suggests a previously undescribed source of modularity and exibility in gene regulation and may play an important role in the evolution of transcriptional regulatory networks. Japan Society for the Promotion of Science (Fellowship for Young Scientists) National Institutes of Health (U.S.) (Grant R01 HG0039850 National Institutes of Health (U.S.) (Molecular Biophysics Training Grant T32 GM008313) 2014-07-10T19:38:29Z 2014-07-10T19:38:29Z 2013-07 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/88252 Nakagawa, S., S. S. Gisselbrecht, J. M. Rogers, D. L. Hartl, and M. L. Bulyk. “DNA-Binding Specificity Changes in the Evolution of Forkhead Transcription Factors.” Proceedings of the National Academy of Sciences 110, no. 30 (July 23, 2013): 12349–12354. en_US http://dx.doi.org/10.1073/pnas.1310430110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Nakagawa, So Gisselbrecht, Stephen S. Rogers, Julia M. Hartl, Daniel L. Bulyk, Martha L. DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title | DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title_full | DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title_fullStr | DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title_full_unstemmed | DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title_short | DNA-binding specificity changes in the evolution of forkhead transcription factors |
| title_sort | dna binding specificity changes in the evolution of forkhead transcription factors |
| url | http://hdl.handle.net/1721.1/88252 |
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