ArticleProceedings of the National Academy of Sciences of the United States of America2008
Activity-dependent repression of muscle genes by NFAT.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Ets2 Is an Activity-Dependent Transcriptional Regulator of a Fast-Twitch Muscle Program.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Extracellular C1qbp inhibits myogenesis by suppressing NFATc1.Scientific reports · 2024Article
- Role and Regulation of Transcription Factors in Osteoclastogenesis.International journal of molecular sciences · 2023Review
- Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.PLoS genetics · 2021Article
- Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.International journal of molecular sciences · 2021Article
- Molecular Mechanisms Mediating Adaptation to Exercise.Advances in experimental medicine and biology · 2020Review
- Physical Activity and Brain Health.Genes · 2019Review
- CaFrontiers in aging neuroscience · 2018Article
- Gα13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.The Journal of clinical investigation · 2017Article
- Properties of skeletal muscle in the teleost Sternopygus macrurus are unaffected by short-term electrical inactivity.Physiological genomics · 2016Article
- The calcineurin-NFAT pathway controls activity-dependent circadian gene expression in slow skeletal muscle.Molecular metabolism · 2015Article
- DNA methylation dynamics in muscle development and disease.Frontiers in aging neuroscience · 2015Review
- NFATc1 controls skeletal muscle fiber type and is a negative regulator of MyoD activity.Cell reports · 2014Article
- Genome-wide DNA methylation changes with age in disease-free human skeletal muscle.Aging cell · 2014Article
- Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle fiber type or size.PloS one · 2014Article
- Mechanisms of muscle gene regulation in the electric organ of Sternopygus macrurus.The Journal of experimental biology · 2013Article
- Calcineurin inhibition and new-onset diabetes mellitus after transplantation.Transplantation · 2013Review
- Nitric oxide synthase inhibition prevents activity-induced calcineurin-NFATc1 signalling and fast-to-slow skeletal muscle fibre type conversions.The Journal of physiology · 2012Article
- PPARδ regulates satellite cell proliferation and skeletal muscle regeneration.Skeletal muscle · 2011Article
- Chronic low-frequency stimulation transforms cat masticatory muscle fibers into jaw-slow fibers.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Adult skeletal muscles retain an adaptive capacity to switch between slow- and fast-twitch properties that largely depend on motoneuron activity. The NFAT (nuclear factor of activated T cells) family of calcium-dependent transcription factors has been implicated in the up-regulation of genes encoding slow contractile proteins in response to slow-patterned motoneuron depolarization. Here, we demonstrate an unexpected, novel function of NFATc1 in slow-twitch muscles. Using the troponin I fast (TnIf) intronic regulatory element (FIRE), we identified sequences that down-regulate its function selectively in response to patterns of electrical activity that mimic slow motoneuron firing. A bona fide NFAT binding site in the TnIf FIRE was identified by site-directed mutations and by electrophoretic mobility and supershift assays. The activity-dependent transcriptional repression of FIRE is mediated through this NFAT site and, importantly, its mutation did not alter the up-regulation of TnIf transcription by fast-patterned activity. siRNA-mediated knockdown of NFATc1 in adult muscles resulted in ectopic activation of the FIRE in the slow soleus, without affecting enhancer activity in the fast extensor digitorum longus muscle. These findings demonstrate that NFAT can function as a repressor of fast contractile genes in slow muscles and they exemplify how an activity pattern can increase or decrease the expression of distinct contractile genes in a use-dependent manner as to enhance phenotypic differences among fiber types or induce adaptive changes in adult muscles.
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Registered trials
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.