Evidence map›Paper›PMID 32352975›Full record

ArticlePLoS genetics2020

Quantitative live imaging of Venus::BMAL1 in a mouse model reveals complex dynamics of the master circadian clock regulator.

Nan Yang, Nicola J Smyllie, Honor Morris, Cátia F Gonçalves, Michal Dudek, Dharshika R J Pathiranage, Johanna E Chesham, Antony Adamson, David G Spiller, Egor Zindy and 6 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  9. Review
  10. 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
  11. Article
  12. Article
  13. Circadian rhythms in colonic function.Frontiers in physiology · 2023
    Review
  14. PRD-2 mediates clock-regulated perinuclear localization of clock gene RNAs within the circadian cycle ofProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Co-regulation of circadian clock genes and microRNAs in bone metabolism.Journal of Zhejiang University. Science. B · 2022
    Review
  16. Article
  17. Cell-Type-Specific Circadian Bioluminescence Rhythms inJournal of biological rhythms · 2022
    Article
  18. Article
  19. Article
  20. Endogenous SORedox biology · 2021
    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

16 authors at 4 institutions in 1 country.

Nan YangWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.
Nicola J SmyllieDivision of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.ORCID 0000-0002-6324-1421
Honor MorrisWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.ORCID 0000-0001-9801-5144
Cátia F GonçalvesWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.ORCID 0000-0001-5221-5458
Michal DudekWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-3152-1127
Dharshika R J PathiranageWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-0701-1880
Johanna E CheshamDivision of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.
Antony AdamsonFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-5408-0013
David G SpillerFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Egor ZindyFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-0033-0002
James BagnallFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Neil HumphreysFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-3210-4093
Judith HoylandFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.ORCID 0000-0003-4876-5208
Andrew S I LoudonFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Michael H HastingsDivision of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.
Qing-Jun MengWellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.ORCID 0000-0002-9426-8336
University of Manchester · GBWellcome Centre for Cell-Matrix Research · GBMRC Laboratory of Molecular Biology · GBManchester Academic Health Science Centre · GB

Funding

Biotechnology and Biological Sciences Research Council BB/P017347/1Medical Research Council MC_U105170643Medical Research Council MR/K019392/1Medical Research Council MR/P010709/1Medical Research Council MR/T016744/1Versus Arthritis 20875Wellcome Trust 088785/Z/09/ZWellcome Trust 107851/Z/15/ZWellcome Trust 215205/Z/19/ZWellcome Trust WT107851/Z/15/Z
6 · The paper itself

Abstract

Evolutionarily conserved circadian clocks generate 24-hour rhythms in physiology and behaviour that adapt organisms to their daily and seasonal environments. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the principal co-ordinator of the cell-autonomous clocks distributed across all major tissues. The importance of robust daily rhythms is highlighted by experimental and epidemiological associations between circadian disruption and human diseases. BMAL1 (a bHLH-PAS domain-containing transcription factor) is the master positive regulator within the transcriptional-translational feedback loops (TTFLs) that cell-autonomously define circadian time. It drives transcription of the negative regulators Period and Cryptochrome alongside numerous clock output genes, and thereby powers circadian time-keeping. Because deletion of Bmal1 alone is sufficient to eliminate circadian rhythms in cells and the whole animal it has been widely used as a model for molecular disruption of circadian rhythms, revealing essential, tissue-specific roles of BMAL1 in, for example, the brain, liver and the musculoskeletal system. Moreover, BMAL1 has clock-independent functions that influence ageing and protein translation. Despite the essential role of BMAL1 in circadian time-keeping, direct measures of its intra-cellular behaviour are still lacking. To fill this knowledge-gap, we used CRISPR Cas9 to generate a mouse expressing a knock-in fluorescent fusion of endogenous BMAL1 protein (Venus::BMAL1) for quantitative live imaging in physiological settings. The Bmal1Venus mouse model enabled us to visualise and quantify the daily behaviour of this core clock factor in central (SCN) and peripheral clocks, with single-cell resolution that revealed its circadian expression, anti-phasic to negative regulators, nuclear-cytoplasmic mobility and molecular abundance.

Indexed as

Circadian RhythmAgingAnimalsARNTL Transcription FactorsBacterial ProteinsBrainCells, CulturedFeedback, PhysiologicalLiverLuminescent ProteinsMiceMicroscopy, FluorescenceMuscle, SkeletalProtein BiosynthesisRecombinant ProteinsSingle-Cell AnalysisARNTL Transcription FactorsBacterial ProteinsBmal1 protein, mouseLuminescent ProteinsRecombinant Proteinsyellow fluorescent protein, Bacteria

Identifiers

PMID32352975
PMCPMC7217492
OpenAlexW3022601824

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.