Rapid evolutionary rewiring of a structurally constrained eye enhancer
Copyright © 2011 Elsevier Ltd. All rights reserved..
BACKGROUND: Enhancers are genomic cis-regulatory sequences that integrate spatiotemporal signals to control gene expression. Enhancer activity depends on the combination of bound transcription factors as well as-in some cases-the arrangement and spacing of binding sites for these factors. Here, we examine evolutionary changes to the sequence and structure of sparkling, a Notch/EGFR/Runx-regulated enhancer that activates the dPax2 gene in cone cells of the developing Drosophila eye.
RESULTS: Despite functional and structural constraints on its sequence, sparkling has undergone major reorganization in its recent evolutionary history. Our data suggest that the relative strengths of the various regulatory inputs into sparkling change rapidly over evolutionary time, such that reduced input from some factors is compensated by increased input from different regulators. These gains and losses are at least partly responsible for the changes in enhancer structure that we observe. Furthermore, stereotypical spatial relationships between certain binding sites ("grammar elements") can be identified in all sparkling orthologs-although the sites themselves are often recently derived. We also find that low binding affinity for the Notch-regulated transcription factor Su(H), a conserved property of sparkling, is required to prevent ectopic responses to Notch in noncone cells.
CONCLUSIONS: Rapid DNA sequence turnover does not imply either the absence of critical cis-regulatory information or the absence of structural rules. Our findings demonstrate that even a severely constrained cis-regulatory sequence can be significantly rewired over a short evolutionary timescale.
| Errataetall: |
CommentIn: Curr Biol. 2011 Jul 26;21(14):R542-3. - PMID 21783031 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Current biology : CB - 21(2011), 14 vom: 26. Juli, Seite 1186-96 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Swanson, Christina I [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.12.2011 Date Revised 20.10.2021 published: Print-Electronic CommentIn: Curr Biol. 2011 Jul 26;21(14):R542-3. - PMID 21783031 Citation Status MEDLINE |
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| doi: |
10.1016/j.cub.2011.05.056 |
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| 500 | |a CommentIn: Curr Biol. 2011 Jul 26;21(14):R542-3. - PMID 21783031 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2011 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: Enhancers are genomic cis-regulatory sequences that integrate spatiotemporal signals to control gene expression. Enhancer activity depends on the combination of bound transcription factors as well as-in some cases-the arrangement and spacing of binding sites for these factors. Here, we examine evolutionary changes to the sequence and structure of sparkling, a Notch/EGFR/Runx-regulated enhancer that activates the dPax2 gene in cone cells of the developing Drosophila eye | ||
| 520 | |a RESULTS: Despite functional and structural constraints on its sequence, sparkling has undergone major reorganization in its recent evolutionary history. Our data suggest that the relative strengths of the various regulatory inputs into sparkling change rapidly over evolutionary time, such that reduced input from some factors is compensated by increased input from different regulators. These gains and losses are at least partly responsible for the changes in enhancer structure that we observe. Furthermore, stereotypical spatial relationships between certain binding sites ("grammar elements") can be identified in all sparkling orthologs-although the sites themselves are often recently derived. We also find that low binding affinity for the Notch-regulated transcription factor Su(H), a conserved property of sparkling, is required to prevent ectopic responses to Notch in noncone cells | ||
| 520 | |a CONCLUSIONS: Rapid DNA sequence turnover does not imply either the absence of critical cis-regulatory information or the absence of structural rules. Our findings demonstrate that even a severely constrained cis-regulatory sequence can be significantly rewired over a short evolutionary timescale | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, American Recovery and Reinvestment Act | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Schwimmer, David B |e verfasserin |4 aut | |
| 700 | 1 | |a Barolo, Scott |e verfasserin |4 aut | |
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