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  • 1
    Online Resource
    Online Resource
    Alternative transcription start sites contribute to acute-stress-induced transcriptome response in human skeletal muscle
    Springer Science and Business Media LLC ; 2022
    In:  Human Genomics Vol. 16, No. 1 ( 2022-12)
    Details
    In: Human Genomics, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2022-12)
    Abstract: More than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress-induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise). Results We identified 44,680 CAGE TSS clusters (including 3764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of “classic” transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors. Conclusions Transcriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.
    Type of Medium: Online Resource
    ISSN: 1479-7364
    URL: Article
    DOI: 10.1186/s40246-022-00399-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2147618-4
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  • 2
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    Regulation of Proteins in Human Skeletal Muscle: The Role of Transcription
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-02-26)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-02-26)
    Abstract: Regular low intensity aerobic exercise (aerobic training) provides effective protection against various metabolic disorders. Here, the roles played by transient transcriptome responses to acute exercise and by changes in baseline gene expression during up-regulation of protein content in human skeletal muscle were investigated after 2 months of aerobic training. Seven untrained males were involved in a 2 month aerobic cycling training program. Mass-spectrometry and RNA sequencing were used to evaluate proteome and transcriptome responses to training and acute exercise. We found that proteins with different functions are regulated differently at the transcriptional level; for example, a training-induced increase in the content of extracellular matrix-related proteins is regulated at the transcriptional level, while an increase in the content of mitochondrial proteins is not. An increase in the skeletal muscle content of several proteins (including mitochondrial proteins) was associated with increased protein stability, which is related to a chaperone-dependent mechanism and/or reduced regulation by proteolysis. These findings increase our understanding of the molecular mechanisms underlying regulation of protein expression in human skeletal muscle subjected to repeated stress (long term aerobic training) and may provide an opportunity to control the expression of specific proteins (e.g., extracellular matrix-related proteins, mitochondrial proteins) through physiological and/or pharmacological approaches.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-60578-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 3
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    Effect of aerobic training on baseline expression of signaling and respiratory proteins in human skeletal muscle
    Wiley ; 2018
    In:  Physiological Reports Vol. 6, No. 17 ( 2018-09), p. e13868-
    Details
    In: Physiological Reports, Wiley, Vol. 6, No. 17 ( 2018-09), p. e13868-
    Type of Medium: Online Resource
    ISSN: 2051-817X
    URL: Article
    DOI: 10.14814/phy2.13868
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2724325-4
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  • 4
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    Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion
    American Physiological Society ; 2023
    In:  Journal of Applied Physiology Vol. 134, No. 5 ( 2023-05-01), p. 1256-1264
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 134, No. 5 ( 2023-05-01), p. 1256-1264
    Abstract: We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25–34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse. NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00048.2023
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2023
    detail.hit.zdb_id: 1404365-8
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    SSG: 31
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  • 5
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    PL-008 Adaptation of skeletal muscle to aerobic exercise: specific transcriptome response to acute exercise and training
    Universite Catholique de Louvain ; 2018
    In:  Exercise Biochemistry Review Vol. 1, No. 1 ( 2018-09-29)
    Details
    In: Exercise Biochemistry Review, Universite Catholique de Louvain, Vol. 1, No. 1 ( 2018-09-29)
    Abstract: Objective Variety of processes including circadian rhythm and systemic factors affect expression of many genes in skeletal muscle during a day. Therefore, post-exercise gene expression depends on many factors: contractile activity per seas well as circadian rhythm, nerve activity, concentration of different substances in blood, feeding and fasting. In our study, we investigated specific for contractile activity changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle in basal state. Methods Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (basal state, 48 h after the previous exercise), 1 and 4 h after one-legged exercise from m. vastus lateralisof either leg. This approach allowed us to evaluate specific changes in the transcriptome associated with contractile activity. RNA­sequencing (84 samples in total; ~42 million reads/sample) was performed by HiSeq 2500 (Illumina). Results Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. After one-legged exercise, expression of many genes was changed in exercised muscle (~1500) as well as in non-exercised muscle (~400). Pronounced changes in gene expression in non-exercised muscle may be associated with many factors, including circadian rhythm (result of GO analysis). To examine transcriptome changes specific for contractile activity, the difference in gene expression between legs was examined. In untrained muscle, one-legged exercise changed expression of ~1200 genes specific for contractile activity at each time point. Despite the same relative intensity of one-legged exercise, transcriptomic response in trained muscle was markedly lower (~300 genes) compare to untrained. We observed a strong overlap between transcriptomic responses (~250 genes) and particularly between enriched transcription factor binding sites in promoters of these genes in untrained and trained muscles. These sets of genes and transcription factors play the key role in adaptation of muscle to contractile activity independently on the level of muscular fitness. Surprisingly, 2 months aerobic training changed the expression of more than 1500 genes in basal state. Noteworthy, these genes demonstrated a small overlap (~200 genes) with genes related to specific response to acute exercise. Moreover, these genes were associated with significantly different biological processes than genes related to specific response to acute exercise. Conclusions Specific for contractile activity changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, the specific transcriptome response to acute exercise become much less pronounced. A computational approach reveals common transcription factors important for adaptation of both untrained and trained muscle. We found out that adaptation of muscle to aerobic training associates not only with the transitory changes in gene expression after each exercise, but also with the marked changes in transcriptome in basal state. This work was supported by the Russian Science Foundation (14­15­00768).
    Type of Medium: Online Resource
    ISSN: 2593-7588
    URL: Issue
    URL: Article
    DOI: 10.14428/ebr.v1i1
    DOI: 10.14428/ebr.v1i1.8113
    Language: Unknown
    Publisher: Universite Catholique de Louvain
    Publication Date: 2018
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  • 6
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    Intensity-dependent gene expression after aerobic exercise in endurance-trained skeletal muscle
    Termedia Sp. z.o.o. ; 2018
    In:  Biology of Sport Vol. 35, No. 3 ( 2018), p. 277-289
    Details
    In: Biology of Sport, Termedia Sp. z.o.o., Vol. 35, No. 3 ( 2018), p. 277-289
    Type of Medium: Online Resource
    ISSN: 0860-021X
    URL: Article
    DOI: 10.5114/biolsport.2018.77828
    Language: Unknown
    Publisher: Termedia Sp. z.o.o.
    Publication Date: 2018
    detail.hit.zdb_id: 2620894-5
    SSG: 31
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  • 7
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    Regulation of PPARGC1A gene expression in trained and untrained human skeletal muscle
    Wiley ; 2017
    In:  Physiological Reports Vol. 5, No. 23 ( 2017-12)
    Details
    In: Physiological Reports, Wiley, Vol. 5, No. 23 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 2051-817X , 2051-817X
    URL: Article
    DOI: 10.14814/phy2.13543
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2724325-4
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  • 8
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    Dysregulation of early gene response to a mixed meal in skeletal muscle in obesity and type 2 diabetes
    American Physiological Society ; 2023
    In:  Physiological Genomics Vol. 55, No. 10 ( 2023-10-01), p. 468-477
    Details
    In: Physiological Genomics, American Physiological Society, Vol. 55, No. 10 ( 2023-10-01), p. 468-477
    Abstract: Obesity- and type 2 diabetes mellitus-induced changes in the expression of protein-coding genes in human skeletal muscle were extensively examined at baseline (after an overnight fast). We aimed to compare the early transcriptomic response to a typical single meal in skeletal muscle of metabolically healthy subjects and obese individuals without and with type 2 diabetes. Transcriptomic response (RNA-seq) to a mixed meal (nutritional drink, ∼25 kJ/kg of body mass) was examined in the vastus lateralis muscle (1 h after a meal) in 7 healthy subjects and 14 obese individuals without or with type 2 diabetes. In all obese individuals, the transcriptome response to a meal was dysregulated (suppressed and altered) and associated with different biological processes compared with healthy control. To search for potential transcription factors regulating transcriptomic response to a meal, the enrichment of transcription factor-binding sites in individual promoters of the human skeletal muscle was examined. In obese individuals, the transcriptomic response is associated with a different set of transcription factors than that in healthy subjects. In conclusion, metabolic disorders are associated with a defect in the regulation of mixed meal/insulin-mediated gene expression-insulin resistance in terms of gene expression. Importantly, this dysregulation occurs in obese individuals without type 2 diabetes, i.e., at the first stage of the development of metabolic disorders. NEW & NOTEWORTHY In skeletal muscle of metabolically healthy subjects, a typical single meal normalized to body mass induces activation of various transcription factors, expression of numerous receptor tyrosine kinases associated with the insulin signaling cascade, and transcription regulators. In skeletal muscle of obese individuals without and with type 2 diabetes, this signaling network is poorly regulated at the transcriptional level, indicating dysregulation of the early gene response to a mixed meal.
    Type of Medium: Online Resource
    ISSN: 1094-8341 , 1531-2267
    URL: Article
    DOI: 10.1152/physiolgenomics.00046.2023
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2023
    detail.hit.zdb_id: 2031330-5
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  • 9
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    Domesticated gag Gene of Drosophila LTR Retrotransposons Is Involved in Response to Oxidative Stress
    MDPI AG ; 2020
    In:  Genes Vol. 11, No. 4 ( 2020-04-06), p. 396-
    Details
    In: Genes, MDPI AG, Vol. 11, No. 4 ( 2020-04-06), p. 396-
    Abstract: Drosophila melanogaster is one of the most extensively used genetic model organisms for studying LTR retrotransposons that are represented by various groups in its genome. However, the phenomenon of molecular domestication of LTR retrotransposons has been insufficiently studied in Drosophila, as well as in other invertebrates. The present work is devoted to studying the role of the domesticated gag gene, Gagr, in the Drosophila genome. The Gagr gene has been shown to be involved in the response to stress caused by exposure to ammonium persulfate, but not in the stress response to oligomycin A, zeomycin, and cadmium chloride. Ammonium persulfate tissue specifically activates the expression of Gagr in the tissues of the carcass, but not in the gut. We found that the Gagr gene promoter contains one binding motif for the transcription factor kayak, a component of the JNK signaling pathway, and two binding motifs for the transcription factor Stat92E, a component of the Jak-STAT signaling pathway. Remarkably, Gagr orthologs contain the second binding motif for Stat92E only in D. melanogaster, D. simulans and D. sechellia, whereas in D. yakuba and D. erecta, Gagr orthologs contain a single motif, and there are no binding sites for Stat92E in the promoters of Gagr orthologs in D. ananassae and in species outside the melanogaster group. The data obtained indicate the formation of the protective function of the Gagr gene during evolution.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes11040396
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
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  • 10
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    Transcriptomic Signatures and Upstream Regulation in Human Skeletal Muscle Adapted to Disuse and Aerobic Exercise
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 3 ( 2021-01-26), p. 1208-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 3 ( 2021-01-26), p. 1208-
    Abstract: Inactivity is associated with the development of numerous disorders. Regular aerobic exercise is broadly used as a key intervention to prevent and treat these pathological conditions. In our meta-analysis we aimed to identify and compare (i) the transcriptomic signatures related to disuse, regular and acute aerobic exercise in human skeletal muscle and (ii) the biological effects and transcription factors associated with these transcriptomic changes. A standardized workflow with robust cut-off criteria was used to analyze 27 transcriptomic datasets for the vastus lateralis muscle of healthy humans subjected to disuse, regular and acute aerobic exercise. We evaluated the role of transcriptional regulation in the phenotypic changes described in the literature. The responses to chronic interventions (disuse and regular training) partially correspond to the phenotypic effects. Acute exercise induces changes that are mainly related to the regulation of gene expression, including a strong enrichment of several transcription factors (most of which are related to the ATF/CREB/AP-1 superfamily) and a massive increase in the expression levels of genes encoding transcription factors and co-activators. Overall, the adaptation strategies of skeletal muscle to decreased and increased levels of physical activity differ in direction and demonstrate qualitative differences that are closely associated with the activation of different sets of transcription factors.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22031208
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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