Evidence map›Paper›PMID 28869038›Full record

ArticleeLife2017

The genomic landscape of human cellular circadian variation points to a novel role for the signalosome.

Ludmila Gaspar, Cedric Howald, Konstantin Popadin, Bert Maier, Daniel Mauvoisin, Ermanno Moriggi, Maria Gutierrez-Arcelus, Emilie Falconnet, Christelle Borel, Dieter Kunz and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Editorial: Rising stars in chronobiology 2022.Frontiers in physiology · 2024
    Article
  2. Steve Brown.Journal of biological rhythms · 2023
    Article
  3. Review
  4. 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

15 authors.

Ludmila GasparInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-6673-7492
Cedric HowaldDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Konstantin PopadinDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.ORCID https://orcid.org/0000-0002-2117-6086
Bert MaierCharité-Universitätsmedizin, Laboratory of Chronobiology, Berlin, Germany.
Daniel MauvoisinDepartment of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0003-0571-0741
Ermanno MoriggiInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-4600-5777
Maria Gutierrez-ArcelusDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Emilie FalconnetDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Christelle BorelDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Dieter KunzInstitute of Physiology, Charité-Universitätsmedizin Berlin, Working Group Sleep Research & Clinical Chronobiology, Berlin, Germany.
Achim KramerCharité-Universitätsmedizin, Laboratory of Chronobiology, Berlin, Germany.
Frederic GachonDepartment of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0002-9279-9707
Emmanouil T DermitzakisDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Stylianos E AntonarakisDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Steven A BrownInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-5511-568X

Funding

European Research Council 260988
6 · The paper itself

Abstract

The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype.

Indexed as

Biological Variation, PopulationCircadian RhythmGene Expression RegulationGenetic VariationARNTL Transcription FactorsCOP9 Signalosome ComplexGenome-Wide Association StudyHumansProteinsProtein StabilityARNTL Transcription FactorsBMAL1 protein, humanCOP9 Signalosome ComplexCOPS8 protein, humanProteinscell biologycircadianfibroblastgenetic variationgenome-wide associationhumanprotein stabilitysignalosome

Identifiers

PMID28869038
PMCPMC5601996

What OpenQuestion holds

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Registered trials

None linked

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.