Evidence map›Paper›PMID 35285799›Full record

ArticleeLife2022

Quantification of protein abundance and interaction defines a mechanism for operation of the circadian clock.

Alex A Koch, James S Bagnall, Nicola J Smyllie, Nicola Begley, Antony D Adamson, Jennifer L Fribourgh, David G Spiller, Qing-Jun Meng, Carrie L Partch, Korbinian Strimmer and 3 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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

29 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  12. From homogeneity to heterogeneity: Refining stochastic simulations of gene regulation.Computational and structural biotechnology journal · 2025
    Article
  13. Review
  14. Review
  15. Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Review
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

13 authors at 3 institutions in 2 countries.

Alex A Koch *Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-0592-331X
James S Bagnall *Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-1735-5855
Nicola J SmyllieMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0002-6324-1421
Nicola BegleyFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-3601-9152
Antony D AdamsonFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-5408-0013
Jennifer L FribourghDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States.
David G SpillerFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-2502-6787
Qing-Jun MengFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-9426-8336
Carrie L PartchDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, United States.ORCID 0000-0002-4677-2861
Korbinian StrimmerDepartment of Mathematics, University of Manchester, Manchester, United Kingdom.ORCID 0000-0001-7917-2056
Thomas A HouseDepartment of Mathematics, University of Manchester, Manchester, United Kingdom.ORCID 0000-0001-5835-8062
Michael H HastingsMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0001-8576-6651
Andrew S I LoudonFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-3648-445X
University of Manchester · GBMRC Laboratory of Molecular Biology · GBUniversity of California, Santa Cruz · US

Funding

Structures and mechanisms of circadian rhythms from cyanobacteria to humansR35GM141849 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI PARTCH, CARRIE L · 2021 to 2025
$4.6M
Exploring the structural basis for 24-hour timekeeping in mammalsR01GM107069 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI PARTCH, CARRIE L · 2013 to 2020
$3.2M
Biotechnology and Biological Sciences Research Council BB/P017347/1Biotechnology and Biological Sciences Research Council BB/P017355/1Medical Research Council MC_U105170643NIGMS NIH HHS R01 GM107069NIGMS NIH HHS R35 GM141849Wellcome Trust 107851/Z/15/ZWellcome Trust 216416/Z/19/Z
6 · The paper itself

Abstract

The mammalian circadian clock exerts control of daily gene expression through cycles of DNA binding. Here, we develop a quantitative model of how a finite pool of BMAL1 protein can regulate thousands of target sites over daily time scales. We used quantitative imaging to track dynamic changes in endogenous labelled proteins across peripheral tissues and the SCN. We determine the contribution of multiple rhythmic processes coordinating BMAL1 DNA binding, including cycling molecular abundance, binding affinities, and repression. We find nuclear BMAL1 concentration determines corresponding CLOCK through heterodimerisation and define a DNA residence time of this complex. Repression of CLOCK:BMAL1 is achieved through rhythmic changes to BMAL1:CRY1 association and high-affinity interactions between PER2:CRY1 which mediates CLOCK:BMAL1 displacement from DNA. Finally, stochastic modelling reveals a dual role for PER:CRY complexes in which increasing concentrations of PER2:CRY1 promotes removal of BMAL1:CLOCK from genes consequently enhancing ability to move to new target sites.

Indexed as

Circadian ClocksAnimalsARNTL Transcription FactorsCircadian RhythmCLOCK ProteinsMammalsARNTL Transcription FactorsCLOCK Proteinscell biologychromosomescircadianDNA bindingFRAPgene expressionlive-cell imagingmodellingmousesingle cell quantification

Identifiers

PMID35285799
PMCPMC8983044
OpenAlexW4221031659

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.