Suboptimization of Developmental Enhancers

Overview

Journal Science

Specialty Science

Date 2015 Oct 17

PMID 26472909

Citations 178

Authors

Emma K Farley

Katrina M Olson

Wei Zhang

Alexander J Brandt

Daniel S Rokhsar

Michael S Levine

Affiliations

Soon will be listed here.

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.

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