Molecular Biology

Remote Enhancement

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Science  16 Apr 2010:
Vol. 328, Issue 5976, pp. 287
DOI: 10.1126/science.328.5976.287-a

Rescuing spa function by moving it closer.

CREDIT: SWANSON ET AL., DEV. CELL 18, 359 (2010)

The temporal and cell type–specific regulation of gene expression relies in part on enhancers, which are noncoding regions of the genome that control tissue-specific expression of a gene sometimes located hundreds of kilobases away. Enhancers recruit regulatory proteins to decondense chromatin and promote the assembly of transcription machinery at genes. Swanson et al. have dissected the 350-bp sparkling (spa) enhancer that controls expression of the dPax2 gene, which specifies cone cell fate in the developing Drosophila eye. The spa enhancer has been shown to consist of 12 binding sites that recruit four regulatory proteins, the combination of which was thought to be sufficient to activate gene expression. By analyzing mutated versions of a synthetic spa enhancer in vivo, the authors have identified additional regulatory regions that are required for gene expression. One of these regions was required only when the enhancer was located 846 bp upstream of the promoter, but not at 121 bp, which suggests that other enhancers may contain similar hidden remote-control regions that work at a distance. Rearranging the regulatory elements in spa switched its cell-type specificity. Thus, both distance and the order of regulatory regions enable enhancers to fine-tune gene expression, revealing more levels of complexity than previously appreciated.

Dev. Cell 18, 359 (2010).

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