IIx myosin heavy chain promoter regulation cannot be characterized in vivo by direct gene transfer

Pandorf, Clay E.; Haddad, Fadia; Qin, Anqi X.; Baldwin, Kenneth M.

doi:10.1152/ajpcell.00221.2007

Cited by 6 publications

(7 citation statements)

References 25 publications

(43 reference statements)

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“…The MyHC genes and their location, along with the corresponding proteins and expresssion patterns are shown in Fig. 1, which summarizes several reports [13][14][15][16] .…”

Section: Muscle Fiber and Myosin Heavy Chainsupporting

confidence: 68%

Regulatory mechanisms of muscle fiber types and their possible interactions with external nutritional stimuli

Nakazato

Tsutaki

2012

JPFSM

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In this review, we briefly summarize muscle fiber types and mechanisms that regulate their expression from nutritional stimulus. To begin with, we introduce genes and their location on myosin heavy chains (MyHC). Next, we show three major transcriptional controls for MyHCs as (1) calcium signaling, (2) AMPK signaling, and (3) miRNA/anti-sense RNA regulations. Following this, we summarize possible nutrients that effect muscle fiber type transformation. The possible contributors are caloric restriction, polyphenols, and high-fat and high-protein diets. We think that nutritional intervention will be a useful way to control muscle fiber type switching. This approach could be adopted by athletes as a means to condition their muscles.

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“…The MyHC genes and their location, along with the corresponding proteins and expresssion patterns are shown in Fig. 1, which summarizes several reports [13][14][15][16] .…”

Section: Muscle Fiber and Myosin Heavy Chainsupporting

confidence: 68%

Regulatory mechanisms of muscle fiber types and their possible interactions with external nutritional stimuli

Nakazato

Tsutaki

2012

JPFSM

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“…For example, the IIx MHC expression is upregulated in a slow muscle fiber type in response to unloading or inactivity (18,23,25,45); whereas, the same IIx MHC expression is also upregulated in a fast muscle in response to overloading and increased activity, such as resistance training (11,22). The upregulation of the IIx gene in response to opposing stimuli in two different muscle types is intriguing and is thought to occur at the transcriptional/pretranslational level (37,38). The exact mechanism behind this regulation is not clear, but it may be the result of both muscle-type-specific factors acting on the genetic apparatus, as well as cross talk between the IIx gene and its adjacent genes (IIa and IIb).…”

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confidence: 99%

Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle

Rinaldi¹,

Haddad²,

Bodell³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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“…This study demonstrates that the exogenous IIb promoter-reporter activity in skeletal muscle simulates the transcription of the endogenous gene as evidenced by the increases in promoter activity paralleling those of the pre-mRNA and mRNA observed in this study and others 9. In contrast, the use of an exogenous IIx promoter construct was not successful in gene transfer experiments in vivo, as its activity did not parallel that of the endogenous gene 10. Thus, studying the regulation of the IIb MHC promoter in the soleus muscle in response to SI represents a practical model system for investigating the regulatory region(s) that are critical for activating fast MHC gene transcription in skeletal muscle undergoing atrophy and phenotype transition.…”

Section: Discussionmentioning

confidence: 46%

Transcriptional regulation of the myosin heavy chain IIB gene in inactive rat soleus

et al. 2009

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The myosin heavy chain (MHC) isoform composition of skeletal muscle is dependent, in part, on the functional demands of the muscle. The rat soleus muscle primarily expresses the slowcontracting type I MHC; however, chronic inactivity increases expression of the faster-contracting type II MHC isoforms. The purpose of this study was to identify the type IIb MHC promoter region(s) that regulate de novo transcription during chronic inactivity of the soleus induced by spinal cord isolation (SI; complete mid-thoracic and high sacral spinal cord transections plus deafferentation). Seven days after SI, transcription of IIb MHC was evidenced by increases in IIb pre-mRNA and mRNA. The activity of an ≈2.2-kb IIb promoter-firefly luciferase reporter plasmid increased in SI soleus over control as compared to that of a promoterless plasmid. Deletion analyses indicated that the regions encompassing −2237 to −1431, −1048 to −461, and −192 to −161 basepairs (bp) each contributed to the increase in transcriptional activity. Moreover, deletions or mutations of AT-rich regions in the proximal −192 bp region abolished the increased promoter activity. These results provide important insights related to how proximal IIb MHC promoter elements regulate the increased expression of the IIb MHC gene in response to inactivity of a predominantly slow postural muscle as it undergoes a remodeling of its phenotype and functional characteristics.

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IIx myosin heavy chain promoter regulation cannot be characterized in vivo by direct gene transfer

Abstract: Pandorf CE, Haddad F, Qin AX, Baldwin KM. IIx myosin heavy chain promoter regulation cannot be characterized in vivo by direct gene transfer.

Cited by 6 publications

References 25 publications

Regulatory mechanisms of muscle fiber types and their possible interactions with external nutritional stimuli

Regulatory mechanisms of muscle fiber types and their possible interactions with external nutritional stimuli

Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle

Transcriptional regulation of the myosin heavy chain IIB gene in inactive rat soleus

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