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  • 1
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 295, No. 1 ( 2008-07), p. R208-R218
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 295, No. 1 ( 2008-07), p. R208-R218
    Abstract: This study investigated the dynamic regulation of IIx-IIb MHC genes in the fast white medial gastrocnemius (WMG) muscle in response to intermittent resistance exercise training (RE), a model associated with a rapid shift from IIb to IIx expression ( 11 ). We investigated the effect of 4 days of RE on the transcriptional activity across the skeletal MHC gene locus in the WMG in female Sprague-Dawley rats. Our results show that RE resulted in significant shifts from IIb to IIx observed at both the pre-mRNA and mRNA levels. An antisense RNA (xII NAT) was detected in the intergenic (IG) region between IIx and IIb, extending across the entire IIx gene and into its promoter. The expression of the xII NAT was positively correlated with IIb pre-mRNA ( R = +0.8), and negatively correlated with IIx pre-mRNA ( R = −0.8). Transcription mapping of the IIx–IIb IG region revealed the generation of sense IIb and xII NATs from a single promoter region. This bidirectional promoter is highly conserved among species and contains several regulatory elements that may be implicated in its regulation. These results suggest that the IIx and the IIb genes are physically and functionally linked via the bidirectional promoter. In order for the IIx MHC gene to be regulated, a feedback mechanism from the IG xII NAT is needed. In conclusion, the IG bidirectional promoter generating antisense RNA appears to be essential for the coordinated regulation of the skeletal muscle MHC genes during dynamic phenotype shifts.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Medicine & Science in Sports & Exercise Vol. 41, No. 5 ( 2009-05), p. 78-79
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 5 ( 2009-05), p. 78-79
    Type of Medium: Online Resource
    ISSN: 0195-9131
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2003
    In:  Journal of Biological Chemistry Vol. 278, No. 39 ( 2003-09), p. 37132-37138
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 278, No. 39 ( 2003-09), p. 37132-37138
    Type of Medium: Online Resource
    ISSN: 0021-9258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
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  • 4
    In: Experimental Physiology, Wiley, Vol. 94, No. 12 ( 2009-12-01), p. 1163-1173
    Type of Medium: Online Resource
    ISSN: 0958-0670
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 1493802-9
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  • 5
    Online Resource
    Online Resource
    American Physiological Society ; 2009
    In:  Journal of Applied Physiology Vol. 107, No. 4 ( 2009-10), p. 1204-1212
    In: Journal of Applied Physiology, American Physiological Society, Vol. 107, No. 4 ( 2009-10), p. 1204-1212
    Abstract: Skeletal muscles, especially weight-bearing muscles, are very sensitive to changes in loading state. The aim of this paper was to characterize the dynamic changes in the unloaded soleus muscle in vivo following a short bout of hindlimb suspension (HS), testing the hypothesis that transcriptional events respond early to the atrophic stimulus. In fact, we observed that after only 1 day of HS, primary transcript levels of skeletal α-actin and type I myosin heavy chain (MHC) genes were significantly reduced by more than 50% compared with ground control levels. The degree of the decline for the mRNA expression of actin and type I MHC lagged behind that of the pre-mRNA levels after 1 day of HS, but by 2 and 7 days of HS, large decreases were observed. Although the faster MHC isoforms, IIx and IIb, began to be expressed in soleus after 1 day of HS, a relatively significant shift in mRNA expression from the slow MHC isoform type I toward these fast MHC isoforms did not emerge until 7 days of HS. One day of HS was sufficient to show significant decreases in mRNA levels of putative signaling factors serum response factor (SRF), suppressor of cytokine signaling-3 (SOCS3), and striated muscle activator of Rho signaling (STARS), although transcription factors yin-yang-1 (YY1) and transcriptional enhancing factor-1 (TEF-1) were not significantly affected by HS. The protein levels of actin and type I MHC were significantly decreased after 2 days of HS, and SRF protein was significantly decreased after 7 days HS. Our results show that after only 1 day of unloading, pre-mRNA and mRNA expression of muscle proteins and muscle-specific signaling factors are significantly reduced, suggesting that the downregulation of the synthesis side of the protein balance equation that occurs in atrophying muscle is initiated rapidly.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 6
    Online Resource
    Online Resource
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Cell Physiology Vol. 297, No. 1 ( 2009-07), p. C6-C16
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 297, No. 1 ( 2009-07), p. C6-C16
    Abstract: Recent advances in chromatin biology have enhanced our understanding of gene regulation. It is now widely appreciated that gene regulation is dependent upon post-translational modifications to the histones which package genes in the nucleus of cells. Active genes are known to be associated with acetylation of histones (H3ac) and trimethylation of lysine 4 in histone H3 (H3K4me3). Using chromatin immunoprecipitation (ChIP), we examined histone modifications at the myosin heavy chain (MHC) genes expressed in fast vs. slow fiber-type skeletal muscle, and in a model of muscle unloading, which results in a shift to fast MHC gene expression in slow muscles. Both H3ac and H3K4me3 varied directly with the transcriptional activity of the MHC genes in fast fiber-type plantaris and slow fiber-type soleus. During MHC transitions with muscle unloading, histone H3 at the type I MHC becomes de-acetylated in correspondence with down-regulation of that gene, while upregulation of the fast type IIx and IIb MHCs occurs in conjunction with enhanced H3ac in those MHCs. Enrichment of H3K4me3 is also increased at the type IIx and IIb MHCs when these genes are induced with muscle unloading. Downregulation of IIa MHC, however, was not associated with corresponding loss of H3ac or H3K4me3. These observations demonstrate the feasibility of using the ChIP assay to understand the native chromatin environment in adult skeletal muscle, and also suggest that the transcriptional state of types I, IIx and IIb MHC genes are sensitive to histone modifications both in different muscle fiber-types and in response to altered loading states.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    American Physiological Society ; 2012
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 302, No. 7 ( 2012-04-01), p. R854-R867
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 302, No. 7 ( 2012-04-01), p. R854-R867
    Abstract: Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2012
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Medicine & Science in Sports & Exercise Vol. 43, No. 5 ( 2011-05), p. 413-
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 5 ( 2011-05), p. 413-
    Type of Medium: Online Resource
    ISSN: 0195-9131
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 9
    Online Resource
    Online Resource
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 292, No. 6 ( 2007-06), p. H3065-H3071
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 292, No. 6 ( 2007-06), p. H3065-H3071
    Abstract: Two genes encoding cardiac myosin heavy chain (MHC) isoforms, β and α, are arranged in tandem 4.5 kb apart. We examined pre-mRNA and mature mRNA levels of β and α genes in control, diabetic (streptozotocin), hypothyroid (propylthiouracil), and hyperthyroid rat hearts and analyzed the naturally occurring antisense (AS) β RNA species that starts in the middle of the 4.5-kb intergenic region and extends upstream to the β-gene promoter. The β and α genes are expressed antithetically in control, diabetic, hypothyroid, and hyperthyroid hearts. Expression of AS β-RNA was positively correlated with α-mRNA and negatively correlated with sense β mRNA. These results support the novel idea of common promoter-regulatory elements situated in the intergenic region that likely control transcription of both sense α and AS β genes and that AS β transcription negatively regulates β-MHC gene expression. To test whether an intergenic promoter drives transcription of AS β RNA, a 1340-bp sequence of the intergenic region was inserted into a luciferase plasmid in the 3′-to-5′ AS direction and was injected into rat ventricle. This promoter was activated in control heart and decreased greatly in response to propylthiouracil and streptozotocin and increased in hyperthyroid rats, similar in pattern to the endogenous AS β RNA. When a putative retinoic acid receptor (RAR) site (a known thyroid hormone receptor cofactor) in this promoter was mutated, the reporter activity was almost abolished in control, propylthiouracil, and streptozotocin hearts. We conclude that there is an intergenic promoter that is active in the AS direction and that the putative RAR element is a vital regulatory site.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 294, No. 1 ( 2008-01), p. H29-H40
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 294, No. 1 ( 2008-01), p. H29-H40
    Abstract: Cardiac myosin heavy chain (MHC) gene expression undergoes a rapid transition from β- to α-MHC during early rodent neonatal development (0–21 days of age). Thyroid hormone (3,5,3′-triiodothyronine, T 3 ) is a major player in this developmental shift; however, the exact mechanism underlying this transition is poorly understood. The goal of this study was to conduct a more thorough analysis of transcriptional activity of the cardiac MHC gene locus during the early postnatal period in the rodent, in order to gain further insight on the regulation of cardiac MHC genes. We analyzed the expression of α- and β-MHC at protein, mRNA, and pre-mRNA levels at birth and 7, 10, 15, and 21 days after birth in euthyroid and hypothyroid rodents. Using novel technology, we also analyzed RNA expression across the cardiac gene locus, and we discovered that the intergenic (IG) region between the two cardiac genes possesses bidirectional transcriptional activity. This IG transcription results in an antisense RNA product as described previously, which is thought to exert an inhibitory effect on β-MHC gene transcription. On the second half of the IG region, sense transcription occurs, resulting in expression of a sense IG RNA that merges with the α-MHC pre-mRNA. This sense IG RNA transcription was detected in the α-MHC gene promoter, approximately −1.8 kb relative to the α-MHC transcription start site. Both sense and antisense IG RNAs were developmentally regulated and responsive to a hypothyroid state ( 11 , 14 ). This novel observation provides more complexity to the cooperative regulation of the two genes, suggesting the involvement of epigenetic processes in the regulation of cardiac MHC gene locus.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477308-9
    SSG: 12
    Location Call Number Limitation Availability
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