Structural rules and complex regulatory circuitry constrain expression of a Notch- and EGFR-regulated eye enhancer
Copyright 2010 Elsevier Inc. All rights reserved..
Enhancers integrate spatiotemporal information to generate precise patterns of gene expression. How complex is the regulatory logic of a typical developmental enhancer, and how important is its internal organization? Here, we examine in detail the structure and function of sparkling, a Notch- and EGFR/MAPK-regulated, cone cell-specific enhancer of the Drosophila Pax2 gene, in vivo. In addition to its 12 previously identified protein-binding sites, sparkling is densely populated with previously unmapped regulatory sequences, which interact in complex ways to control gene expression. One segment is essential for activation at a distance, yet dispensable for other activation functions and for cell type patterning. Unexpectedly, rearranging sparkling's regulatory sites converts it into a robust photoreceptor-specific enhancer. Our results show that a single combination of regulatory inputs can encode multiple outputs, and suggest that the enhancer's organization determines the correct expression pattern by facilitating certain short-range regulatory interactions at the expense of others.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2010 |
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Erschienen: |
2010 |
Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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Enthalten in: |
Developmental cell - 18(2010), 3 vom: 16. März, Seite 359-70 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Swanson, Christina I [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 12.04.2010 Date Revised 19.04.2024 published: Print Citation Status MEDLINE |
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doi: |
10.1016/j.devcel.2009.12.026 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM195806352 |
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520 | |a Copyright 2010 Elsevier Inc. All rights reserved. | ||
520 | |a Enhancers integrate spatiotemporal information to generate precise patterns of gene expression. How complex is the regulatory logic of a typical developmental enhancer, and how important is its internal organization? Here, we examine in detail the structure and function of sparkling, a Notch- and EGFR/MAPK-regulated, cone cell-specific enhancer of the Drosophila Pax2 gene, in vivo. In addition to its 12 previously identified protein-binding sites, sparkling is densely populated with previously unmapped regulatory sequences, which interact in complex ways to control gene expression. One segment is essential for activation at a distance, yet dispensable for other activation functions and for cell type patterning. Unexpectedly, rearranging sparkling's regulatory sites converts it into a robust photoreceptor-specific enhancer. Our results show that a single combination of regulatory inputs can encode multiple outputs, and suggest that the enhancer's organization determines the correct expression pattern by facilitating certain short-range regulatory interactions at the expense of others | ||
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650 | 7 | |a ErbB Receptors |2 NLM | |
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700 | 1 | |a Barolo, Scott |e verfasserin |4 aut | |
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