ArticlePLoS biology2008
Evolution acts on enhancer organization to fine-tune gradient threshold readouts.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 96 citations in OpenAlex.
- Genome architecture shapes the evolutionary origins of redundant enhancers in fly and mouse.bioRxiv : the preprint server for biology · 2026Article
- Diversity ofFrontiers in cell and developmental biology · 2025Article
- Perspective on recent developments and challenges in regulatory and systems genomics.Bioinformatics advances · 2025Review
- Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation.Developmental cell · 2023Article
- The nested embryonic dorsal domains of BMP-target genes are not scaled to size during the evolution of Drosophila species.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Article
- Article
- DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers.Nature genetics · 2022Article
- Deciphering enhancer sequence using thermodynamics-based models and convolutional neural networks.Nucleic acids research · 2021Article
- Enhancer grammar in development, evolution, and disease: dependencies and interplay.Developmental cell · 2021Review
- Learning and interpreting the gene regulatory grammar in a deep learning framework.PLoS computational biology · 2020Article
- Article
- Stepwise Progression of Embryonic Patterning.Trends in genetics : TIG · 2016Review
- Article
- Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors.Nature genetics · 2016Article
- The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila.G3 (Bethesda, Md.) · 2015Article
- Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence.PLoS genetics · 2015Article
- The evolutionary origination and diversification of a dimorphic gene regulatory network through parallel innovations in cis and trans.PLoS genetics · 2015Article
- Article
- Su(H)-mediated repression positions gene boundaries along the dorsal-ventral axis of Drosophila embryos.Developmental cell · 2014Article
- Absence of a simple code: how transcription factors read the genome.Trends in biochemical sciences · 2014Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. We are therefore exploring the structure and organizational constraints of regulatory sequences by studying functionally equivalent cis-regulatory modules (CRMs) that have been evolving in parallel across several loci. Such an independent dataset allows a multi-locus study that is not hampered by nonfunctional or constrained homology. The neurogenic ectoderm enhancers (NEEs) of Drosophila melanogaster are one such class of coordinately regulated CRMs. The NEEs share a common organization of binding sites and as a set would be useful to study the relationship between CRM organization and CRM activity across evolving lineages. We used the D. melanogaster transgenic system to screen for functional adaptations in the NEEs from divergent drosophilid species. We show that the individual NEE modules across a genome in any one lineage have independently evolved adaptations to compensate for lineage-specific developmental and/or genomic changes. Specifically, we show that both the site composition and the site organization of NEEs have been finely tuned by distinct, lineage-specific selection pressures in each of the three divergent species that we have examined: D. melanogaster, D. pseudoobscura, and D. virilis. Furthermore, by precisely altering the organization of NEEs with different morphogen gradient threshold readouts, we show that CRM organizational evolution is sufficient for explaining changes in enhancer activity. Thus, evolution can act on CRM organization to fine-tune morphogen gradient threshold readouts over a wide dynamic range. Our study demonstrates that equivalence classes of CRMs are powerful tools for detecting lineage-specific adaptations by gene regulatory sequences.
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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.