Suboptimization of developmental enhancers

Emma K. Farley, Katrina M. Olson, Wei Zhang, Alexander J. Brandt, Daniel S. Rokhsar, Michael S. Levine

Research output: Contribution to journalArticlepeer-review

196 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)325-328
Number of pages4
Issue number6258
StatePublished - Oct 16 2015

All Science Journal Classification (ASJC) codes

  • General


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