Article

Enhancer-promoter communication at the Drosophila engrailed locus.

Laboratory of Molecular Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Development (impact factor: 6.6). 09/2009; 136(18):3067-75. DOI:10.1242/dev.036426 pp.3067-75
Source: PubMed

ABSTRACT Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene. How do they know which gene to activate? We have used homing P[en] constructs to study the enhancer-promoter communication at the engrailed locus. Here we show that engrailed enhancers can act over large distances, even skipping over other transcription units, choosing the engrailed promoter over those of neighboring genes. This specificity is achieved in at least three ways. First, early acting engrailed stripe enhancers exhibit promoter specificity. Second, a proximal promoter-tethering element is required for the action of the imaginal disc enhancer(s). Our data suggest that there are two partially redundant promoter-tethering elements. Third, the long-distance action of engrailed enhancers requires a combination of the engrailed promoter and sequences within or closely linked to the promoter proximal Polycomb-group response elements. These data show that multiple mechanisms ensure proper enhancer-promoter communication at the Drosophila engrailed locus.

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  • Article: Dynamic regulation by polycomb group protein complexes controls pattern formation and the cell cycle in Drosophila.
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    ABSTRACT: Polycomb group (PcG) proteins form conserved regulatory complexes that modify chromatin to repress transcription. Here, we report genome-wide binding profiles of PhoRC, the Drosophila PcG protein complex containing the DNA-binding factor Pho/dYY1 and dSfmbt. PhoRC constitutively occupies short Polycomb response elements (PREs) of a large set of developmental regulator genes in both embryos and larvae. The majority of these PREs are co-occupied by the PcG complexes PRC1 and PRC2. Analysis of PcG mutants shows that the PcG system represses genes required for anteroposterior, dorsoventral, and proximodistal patterning of imaginal discs and that it also represses cell cycle regulator genes. Many of these genes are regulated in a dynamic manner, and our results suggest that the PcG system restricts signaling-mediated activation of target genes to appropriate cells. Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants.
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Keywords

activate
 
Drosophila engrailed locus
 
engrailed enhancers
 
engrailed locus
 
engrailed promoter
 
engrailed stripe enhancers exhibit promoter specificity
 
enhancer-promoter communication
 
Enhancers
 
homing P[en] constructs
 
imaginal disc enhancer(s)
 
large distances
 
long-distance action
 
multiple mechanisms
 
promoter proximal Polycomb-group response elements
 
proper enhancer-promoter communication
 
proximal promoter-tethering element
 

Deborah Kwon