ArticleScience (New York, N.Y.)2015
Suboptimization of developmental enhancers.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
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Who cites it
210 citing papers in PubMed.
- Cooperativity enables widespread role of low-affinity motifs in chromatin accessibility and increases regulatory potential.Cell genomics · 2026Article
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Genome-Wide Identification and Characterization of bHLH Family inLife (Basel, Switzerland) · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Amplification of MED30 at chromosome 8q24 reprograms MYC binding to low-affinity oncogenic enhancers in cancer cells.Cell reports · 2026Article
- Combinatorial pioneer transcription factor binding reinforces bivalent epigenetic states to preserve lineage fidelity.bioRxiv : the preprint server for biology · 2026Article
- Review
- Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.bioRxiv : the preprint server for biology · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Functional genomics analysis of developing zebrafish and human endoderm reveals highly conservedGenome research · 2026Article
- CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.Nature communications · 2026Article
- Sequence-based modeling of low-affinity transcription factor-DNA binding through deep learning.NAR genomics and bioinformatics · 2026Article
- Quantitative modulation of a spatial enhancer through the biophysical properties of a transcription factor binding site.Science advances · 2026Article
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
- Article
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Teamwork of clustered low-affinity κB sites and accessory factors regulates transcriptional strength of NF-κB RelA dimers.Nucleic acids research · 2025Article
- Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.Cell reports · 2025Article
- Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable machine learning.Nucleic acids research · 2025Article
- Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication.Cell reports · 2025Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.