Evidence map›Paper›PMID 26344774›Full record

ArticleCell reports2015

Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers.

Zeba Wunderlich, Meghan D J Bragdon, Ben J Vincent, Jonathan A White, Javier Estrada, Angela H DePace

Erratum issuedAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cis-Regulatory Elements in Mammals.International journal of molecular sciences · 2023
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Enhancer redundancy in development and disease.Nature reviews. Genetics · 2021
    Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Zeba WunderlichDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Meghan D J BragdonDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Ben J VincentDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Jonathan A WhiteSwarthmore College, Swarthmore, PA 19081, USA.
Javier EstradaDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Angela H DePaceDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: angela_depace@hms.harvard.edu.

Funding

Drosophila Transgenic RNAi Resource ProjectR01GM084947 · NIGMS · HARVARD MEDICAL SCHOOL · PI PERRIMON, NORBERT · 2008 to 2019
$9.8M
Multi-scale modeling of genetic variation in a developmental networkU01GM103804 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DEPACE, ANGELA H, MARJORAM, PAUL · 2013 to 2016
$2.0M
Dissecting expression divergence in developmental networks across DrosophilidsR00HD073191 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI WUNDERLICH, ZEBA B · 2015 to 2017
$745k
Dissecting expression divergence in developmental networks across DrosophilidsK99HD073191 · NICHD · HARVARD MEDICAL SCHOOL · PI WUNDERLICH, ZEBA B · 2012 to 2013
$258k
NICHD NIH HHS K99 HD073191NICHD NIH HHS K99/R00 HD073191NICHD NIH HHS R00 HD073191NIGMS NIH HHS R01 GM084947NIGMS NIH HHS U01 GM103804NIGMS NIH HHS U01 GM103804-01A1
6 · The paper itself

Abstract

Many developmental genes are controlled by shadow enhancers—pairs of enhancers that drive overlapping expression patterns. We hypothesized that compensatory evolution can maintain the total expression of a gene, while individual shadow enhancers diverge between species. To test this hypothesis, we analyzed expression driven by orthologous pairs of shadow enhancers from Drosophila melanogaster, Drosophila yakuba, and Drosophila pseudoobscura that control expression of Krüppel, a transcription factor that patterns the anterior-posterior axis of blastoderm embryos. We found that the expression driven by the pair of enhancers is conserved between these three species, but expression levels driven by the individual enhancers are not. Using sequence analysis and experimental perturbation, we show that each shadow enhancer is regulated by different transcription factors. These results support the hypothesis that compensatory evolution can occur between shadow enhancers, which has implications for mechanistic and evolutionary studies of gene regulation.

Indexed as

Enhancer Elements, GeneticAnimalsDrosophilaDrosophila ProteinsFemaleGene Expression Regulation, DevelopmentalKruppel-Like Transcription FactorsMaleDrosophila ProteinsKr protein, DrosophilaKruppel-Like Transcription Factors

Identifiers

PMID26344774
PMCPMC4581983

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Registered trials

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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.