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Suboptimization of developmental enhancers

Author(s): Farley, Emma K.; Olson, Katrina M.; Zhang, Wei; Brandt, Alexander J.; Rokhsar, Daniel S.; et al

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Abstract: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities (“suboptimization”). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain “superenhancers,” circumvent this trade-off in specificity and activity.
Publication Date: 16-Oct-2015
Electronic Publication Date: 15-Oct-2015
Citation: Farley, EK, Olson, KM, Zhang, W, Brandt, AJ, Rokhsar, DS, Levine, MS. (2015). Suboptimization of developmental enhancers. Science, 350 (6258), 325 - 328. doi:10.1126/science.aac6948
DOI: doi:10.1126/science.aac6948
ISSN: 0036-8075
EISSN: 1095-9203
Pages: 325 - 328
Type of Material: Journal Article
Journal/Proceeding Title: Science
Version: Author's manuscript

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