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Dev Cell. 2010 Mar 16;18(3):359-70. doi: 10.1016/j.devcel.2009.12.026.

Structural rules and complex regulatory circuitry constrain expression of a Notch- and EGFR-regulated eye enhancer.

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  • 1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

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.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:
20230745
[PubMed - indexed for MEDLINE]
PMCID:
PMC2847355
Free PMC Article

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