Evidence map›Paper›PMID 20956306›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function.

Jessica L Andrews, Xiping Zhang, John J McCarthy, Erin L McDearmon, Troy A Hornberger, Brenda Russell, Kenneth S Campbell, Sandrine Arbogast, Michael B Reid, John R Walker and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.

0numbers the graph read from it
0cells of the map it votes in
232citing papers in PubMed
5.1field-weighted citation impact, top 3% 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

232 citing papers in PubMed, 378 citations in OpenAlex.

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  11. Co-expression network analysis reveals repression ofbioRxiv : the preprint server for biology · 2026
    Article
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  16. New insights into the skeletal muscle circadian clock in ruminants.Journal of animal science and biotechnology · 2026
    Review
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172 more citing papers are in PubMed but not listed here.

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 6 institutions in 1 country.

Jessica L AndrewsSchool of Kinesiology, University of Illinois, Chicago, IL 60609, USA.
Xiping Zhang
John J McCarthy
Erin L McDearmon
Troy A Hornberger
Brenda Russell
Kenneth S Campbell
Sandrine Arbogast
Michael B Reid
John R Walker
John B Hogenesch
Joseph S Takahashi
Karyn A Esser
University of Kentucky · USUniversity of Illinois Chicago · USGenomics Institute of the Novartis Research Foundation · USHoward Hughes Medical Institute · USThe University of Texas Southwestern Medical Center · USUniversity of Pennsylvania · US

Funding

Mouse Mutagenesis: Phenotype-Driven Neuroscience ScreensU01MH061915 · NIMH · NORTHWESTERN UNIVERSITY · PI TAKAHASHI, JOSEPH S · 2001 to 2005
$29.1M
Chemical and Genetic Manipulation of Circadian SystemsP50MH074924 · NIMH · NORTHWESTERN UNIVERSITY · PI TAKAHASHI, JOSEPH S · 2005 to 2009
$10.4M
PHYSIOLOGY OF THE RESPIRATORY MUSCLESR01HL045721 · NHLBI · UNIVERSITY OF KENTUCKY · PI REID, MICHAEL B · 1992 to 2006
$2.1M
Circadian rhythms and skeletal muscleR01AR055246 · NIAMS · UNIVERSITY OF KENTUCKY · PI ESSER, KARYN A · 2008 to 2012
$1.6M
Circadian Regulation of Myod1 TranscriptionR03AR053641 · NIAMS · UNIVERSITY OF KENTUCKY · PI MCCARTHY, JOHN JOSEPH · 2007 to 2009
$217k
Circadian rhythms in skeletal muscle: Role of BmalR21AR050717 · NIAMS · UNIVERSITY OF KENTUCKY · PI ESSER, KARYN ANN · 2003 to 2004
$140k
Howard Hughes Medical InstituteNHLBI NIH HHS HL45721NHLBI NIH HHS R01 HL045721NIAMS NIH HHS AR050717NIAMS NIH HHS AR053641NIAMS NIH HHS R01 AR055246NIAMS NIH HHS R03 AR053641NIAMS NIH HHS R21 AR050717NIMH NIH HHS P50 MH074924NIMH NIH HHS U01 MH061915NIMH NIH HHS U01 MH61915
6 · The paper itself

Abstract

MyoD, a master regulator of myogenesis, exhibits a circadian rhythm in its mRNA and protein levels, suggesting a possible role in the daily maintenance of muscle phenotype and function. We report that MyoD is a direct target of the circadian transcriptional activators CLOCK and BMAL1, which bind in a rhythmic manner to the core enhancer of the MyoD promoter. Skeletal muscle of Clock(Δ19) and Bmal1(-/-) mutant mice exhibited ∼30% reductions in normalized maximal force. A similar reduction in force was observed at the single-fiber level. Electron microscopy (EM) showed that the myofilament architecture was disrupted in skeletal muscle of Clock(Δ19), Bmal1(-/-), and MyoD(-/-) mice. The alteration in myofilament organization was associated with decreased expression of actin, myosins, titin, and several MyoD target genes. EM analysis also demonstrated that muscle from both Clock(Δ19) and Bmal1(-/-) mice had a 40% reduction in mitochondrial volume. The remaining mitochondria in these mutant mice displayed aberrant morphology and increased uncoupling of respiration. This mitochondrial pathology was not seen in muscle of MyoD(-/-) mice. We suggest that altered expression of both Pgc-1α and Pgc-1β in Clock(Δ19) and Bmal1(-/-) mice may underlie this pathology. Taken together, our results demonstrate that disruption of CLOCK or BMAL1 leads to structural and functional alterations at the cellular level in skeletal muscle. The identification of MyoD as a clock-controlled gene provides a mechanism by which the circadian clock may generate a muscle-specific circadian transcriptome in an adaptive role for the daily maintenance of adult skeletal muscle.

Indexed as

AnimalsARNTL Transcription FactorsCircadian ClocksCLOCK ProteinsElectron Microscope TomographyGene Expression ProfilingGene Expression RegulationMiceMice, Inbred BALB CMice, KnockoutMitochondria, MuscleMuscle DevelopmentMuscle, SkeletalMyoD ProteinPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaTrans-ActivatorsARNTL Transcription FactorsBmal1 protein, mouseClock protein, mouseCLOCK ProteinsMyoD1 myogenic differentiation proteinMyoD ProteinPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseTrans-ActivatorsTranscription Factors

Identifiers

PMID20956306
PMCPMC2973897
OpenAlexW2053866174

What OpenQuestion holds

Textmetadata
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.