Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression
During development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interact...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/37545 |
| _version_ | 1828167347935903744 |
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| author | C Matthew Hope Jemma L Webber Sherzod A Tokamov Ilaria Rebay |
| author_facet | C Matthew Hope Jemma L Webber Sherzod A Tokamov Ilaria Rebay |
| author_sort | C Matthew Hope |
| collection | DOAJ |
| description | During development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interactions among transcription factors are also critical, yet how their affinities impact enhancer output is not understood. The Drosophila transcription factor Yan provides a well-suited model to address this, as its function depends on the coordinated activities of two independent and essential domains: the DNA-binding ETS domain and the self-associating SAM domain. To explore how protein–protein affinity influences Yan function, we engineered mutants that increase SAM affinity over four orders of magnitude. This produced a dramatic subcellular redistribution of Yan into punctate structures, reduced repressive output and compromised survival. Cell-type specification and genetic interaction defects suggest distinct requirements for polymerization in different regulatory decisions. We conclude that tuned protein–protein interactions enable the dynamic spectrum of complexes that are required for proper regulation. |
| first_indexed | 2024-04-12T02:16:11Z |
| format | Article |
| id | doaj.art-f26c42e5de834b5897f0e554eed7eaed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:16:11Z |
| publishDate | 2018-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f26c42e5de834b5897f0e554eed7eaed2022-12-22T03:52:15ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.37545Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repressionC Matthew Hope0Jemma L Webber1Sherzod A Tokamov2Ilaria Rebay3https://orcid.org/0000-0002-2444-3864Department of Biochemistry and Molecular Biophysics, University of Chicago, Chicago, United StatesBen May Department for Cancer Research, University of Chicago, Chicago, United StatesCommittee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, United StatesBen May Department for Cancer Research, University of Chicago, Chicago, United States; Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, United StatesDuring development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interactions among transcription factors are also critical, yet how their affinities impact enhancer output is not understood. The Drosophila transcription factor Yan provides a well-suited model to address this, as its function depends on the coordinated activities of two independent and essential domains: the DNA-binding ETS domain and the self-associating SAM domain. To explore how protein–protein affinity influences Yan function, we engineered mutants that increase SAM affinity over four orders of magnitude. This produced a dramatic subcellular redistribution of Yan into punctate structures, reduced repressive output and compromised survival. Cell-type specification and genetic interaction defects suggest distinct requirements for polymerization in different regulatory decisions. We conclude that tuned protein–protein interactions enable the dynamic spectrum of complexes that are required for proper regulation.https://elifesciences.org/articles/37545ETS repressorphotoreceptoreye developmentmathematical modelingreceptor tyrosine kinase signaling |
| spellingShingle | C Matthew Hope Jemma L Webber Sherzod A Tokamov Ilaria Rebay Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression eLife ETS repressor photoreceptor eye development mathematical modeling receptor tyrosine kinase signaling |
| title | Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression |
| title_full | Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression |
| title_fullStr | Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression |
| title_full_unstemmed | Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression |
| title_short | Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression |
| title_sort | tuned polymerization of the transcription factor yan limits off dna sequestration to confer context specific repression |
| topic | ETS repressor photoreceptor eye development mathematical modeling receptor tyrosine kinase signaling |
| url | https://elifesciences.org/articles/37545 |
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