Evidence map›Paper›PMID 26519295›Full record

ArticleBMC genomics2015

Functionally conserved enhancers with divergent sequences in distant vertebrates.

Song Yang, Nir Oksenberg, Sachiko Takayama, Seok-Jin Heo, Alexander Poliakov, Nadav Ahituv, Inna Dubchak, Dario Boffelli

Abstract read
In one paragraph

Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Transcriptional enhancers and their communication with gene promoters.Cellular and molecular life sciences : CMLS · 2021
    Review
  10. Article
  11. Article
  12. Enhancer RNAs are an important regulatory layer of the epigenome.Nature structural & molecular biology · 2020
    Review
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Song YangGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. syang@enders.tch.harvard.edu.
Nir OksenbergDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94158, USA. niroksenberg@gmail.com.
Sachiko TakayamaChildren's Hospital Oakland Research Institute, Oakland, CA, 94609, USA. sachiko.takayama@gmail.com.
Seok-Jin HeoChildren's Hospital Oakland Research Institute, Oakland, CA, 94609, USA. sheo@chori.org.
Alexander PoliakovUS Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA. AVPoliakov@lbl.gov.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94158, USA. nadav.ahituv@ucsf.edu.
Inna DubchakGenomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. ildubchak@lbl.gov.
Dario BoffelliChildren's Hospital Oakland Research Institute, Oakland, CA, 94609, USA. dboffelli@chori.org.

Funding

PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KWOK, PUI-YAN · 2010 to 2014
$16.3M
Comparative Genomics of Non-Coding Regions to Facilitate Translational ResearchR01HL091495 · NHLBI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI DUBCHAK, INNA · 2009 to 2012
$3.2M
Characterization of regulatory elements leading to human limb malformationsR01HD059862 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2013
$2.2M
Massively parallel, in vivo functional testing of regulatory elementsR01HG006768 · NHGRI · UNIVERSITY OF WASHINGTON · PI AHITUV, NADAV, SHENDURE, JAY ASHOK · 2012 to 2014
$1.8M
Computational & Functional Annotation of the Zebrafish Genome Regulatory ToolboxR01HG005058 · NHGRI · STANFORD UNIVERSITY · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2012
$1.6M
Identification & functional characterization of SIM1 obesity-associated variantsR01DK090382 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, VAISSE, CHRISTIAN · 2012 to 2015
$1.3M
Characterization of neuronal gene regulatory elements associated with epilepsyR01NS079231 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV · 2012 to 2015
$1.2M
NHGRI NIH HHS 1R01HG006768NHGRI NIH HHS R01 HG005058NHGRI NIH HHS R01HG005058NHGRI NIH HHS R01 HG006768NHLBI NIH HHS R01 HL091495NICHD NIH HHS R01 HD059862NICHD NIH HHS R01HD059862NIDDK NIH HHS 1R01DK090382NIDDK NIH HHS R01 DK090382NIGMS NIH HHS GM61390NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390NINDS NIH HHS 1R01NS079231NINDS NIH HHS R01 NS079231
6 · The paper itself

Abstract

backgroundTo examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. Our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.

resultsWe searched for sequences that were conserved within groups of closely related species but not between groups of more distant species, and were associated with an epigenetic mark of enhancer activity. To facilitate inferring orthology between non-conserved sequences, we limited our search to introns whose orthology could be unambiguously established by mapping the bracketing exons. We show that a subset of these non-conserved but syntenic sequences from the mouse and zebrafish genomes have homologous functions in a zebrafish transgenic enhancer assay. The conserved expression patterns driven by these enhancers are probably associated with short transcription factor-binding motifs present in the divergent sequences.

conclusionsWe have identified numerous potential enhancers with divergent sequences but a conserved function. These results indicate that selection on function, rather than sequence, may be a common mode of enhancer evolution; evidence for selection at the sequence level is not a necessary criterion to define a gene regulatory element.

Indexed as

Conserved SequenceEnhancer Elements, GeneticGenetic VariationAnimalsAnimals, Genetically ModifiedBinding SitesComputational BiologyEvolution, MolecularGene Expression ProfilingGenome-Wide Association StudyNucleotide MotifsPosition-Specific Scoring MatricesProtein BindingReproducibility of ResultsTranscription FactorsVertebratesTranscription Factors

Identifiers

PMID26519295
PMCPMC4628251

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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.