Structural and functional analysis of myostatin-2 promoter alleles from the marine fish Sparus aurata: Evidence for strong muscle-specific promoter activity and post-transcriptional regulation

Nadjar-Boger, Elisabeth; Hinits, Yaniv; Funkenstein, Bruria

doi:10.1016/j.mce.2012.03.017

Cited by 12 publications

(5 citation statements)

References 67 publications

(86 reference statements)

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“…Such expression patterns are suggestive of a functional divergence among fishes, as the single mammalian myostatin ortholog is predominately expressed in muscle. To identify potential mechanisms responsible for changes in spatial and temporal expression patterns, numerous studies have investigated the promoter region of myostatin in mammals and fish to characterize putative transcription factor binding sites and hormone response elements (Allen and Du, 2008; Funkenstein et al, 2009b; Gabillard et al, 2013; Garikipati et al, 2007; Garikipati et al, 2006; Hu et al, 2013; Li et al, 2012a; Li et al, 2012b; Li et al, 2012c; Ma et al, 2001a; Nadjar-Boger et al, 2012; Nadjar-Boger et al, 2013; Ostbye et al, 2007a; Rodgers and Garikipati, 2008; Spiller et al, 2002; Xue et al, 2012). Putative E-box protein, myogenic regulatory factor (MRF), and myocyte enhancing factor (MEF) binding motifs and glucocorticoid response elements (GREs) appear to be highly conserved components of the myostatin promoter in vertebrates (Rodgers and Garikipati, 2008).…”

Section: Introductionmentioning

confidence: 99%

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

Galt

Froehlich

Remily

et al. 2014

Comparative Biochemistry and Physiology Part A: Molecular &

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Glucocorticoids (GCs) strongly regulate myostatin transcript levels in mammals via glucocorticoid response elements (GREs) in the myostatin promoter, and bioinformatics methods suggest that this regulatory mechanism is conserved among many vertebrates. However, the multiple myostatin genes found in some fishes may be an exception. In rainbow trout (Oncorhynchus mykiss), two genome duplication events have produced three putatively functional myostatin genes, myostatin-1a, -1b and -2a, which are ubiquitously and differentially expressed. In addition, in silico promoter analyses of the rainbow trout myostatin promoters have failed to identify putative GREs, suggesting a divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA expression is not regulated by glucocorticoids in rainbow trout. In this study, both juvenile rainbow trout and primary trout myoblasts were treated with cortisol to examine the relationship between this glucocorticoid and myostatin mRNA expression. Results suggest that exogenous cortisol does not regulate myostatin-1a and -1b expression in vivo, as myostatin mRNA levels were not significantly affected by cortisol treatment in either red or white muscle tissue. In red muscle, myostatin-2a levels were significantly elevated in the cortisol treatment group relative to the control, but not the vehicle control, at both 12 h and 24 h post-injection. As such, it is unclear if cortisol was acting alone or in combination with the vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in vitro. Further work is needed to determine if this response is the direct result of cortisol acting on the myostatin-1b promoter or through an alternative mechanism. These results suggest that regulation of myostatin by cortisol may not be as highly conserved as previously thought and support previous work that describes potential functional divergence of the multiple myostatin genes in fishes.

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Section: Introductionmentioning

confidence: 99%

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

Galt

Froehlich

Remily

et al. 2014

Comparative Biochemistry and Physiology Part A: Molecular &

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“…Deng et al reported that the deletion of -1519 to -1236 bp of 5’-upstream of the pig myostatin promoter increased the promoter transcriptional activity in myoblast cells [ 35 ]. The -1716 to -1850 bp of 5’-upstream of Sparus aurata myostatin 2 promoter was identified as a negative regulatory region [ 36 ]. However, none of these studies identified a specific negative motif at the myostatin promoter.…”

Section: Discussionmentioning

confidence: 99%

Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides)

et al. 2017

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Myostatin is a negative regulator of myogenesis and has been suggested to be an important factor in the development of muscle wasting during viral infection. The objective of this study was to characterize the main regulatory element of the grouper myostatin promoter and to study changes in promoter activity due to viral stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a positive cis-and trans-regulation motif, and an essential binding site for MyoD. In contrast, the E-box E5 is a dominant negative cis-regulatory. The characteristics of grouper myostatin promoter are similar in regulation of muscle growth to that of other species, but mainly through specific regulatory elements. According to these results, we conducted a study to investigate the effect of viral infection on myostatin promoter activity and its regulation. The nervous necrosis virus (NNV) treatment significantly induced myostatin promoter activity. The present study is the first report describing that specific myostatin motifs regulate promoter activity and response to viral infection.

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“…All three alleles were shown to have high sequence identity in the most proximal 1050 bp, while divergence was observed distally. Phylogenetic analysis revealed that mstn-2a and mstn-2b are more closely related than mstn-2c [85]. As for populational frequency, different rates were observed, such that mstn-2b was shown to be more frequent, followed by mstn-2c , while mstn-2a was rather rare and found only in a heterozygous state [84].…”

Section: Fish Mstn Gene Promotermentioning

confidence: 99%

“…As for populational frequency, different rates were observed, such that mstn-2b was shown to be more frequent, followed by mstn-2c , while mstn-2a was rather rare and found only in a heterozygous state [84]. The search for TFBSs showed the presence of potential sites for TATA binding protein and a CAAT box in the proximal promoter, among others [85] (see Additional file 1). The three variants present five conserved E-boxes in the proximal region, and additional E-boxes were identified in allele mstn-2a (five extra sites) and mstn-2b (six extra sites).…”

Section: Fish Mstn Gene Promotermentioning

confidence: 99%

“…In vivo experiments using zebrafish embryo injection of GFP reporter constructs directed by the different promoter alleles as well as luciferase assays of intramuscular injections confirmed the ability of these sequences to drive gene expression, in muscle and non-muscle tissues. Although all alleles functioned as promoters, allele mstn-2b was shown to be stronger than mstn-2a and mstn-2c in driving gene activity [85]. Knowing that mstn-2b allele presents a higher activity, it would be interesting to identify exactly the molecular mechanisms responsible for that difference.…”

Section: Fish Mstn Gene Promotermentioning

confidence: 99%

See 1 more Smart Citation

Myostatin gene promoter: structure, conservation and importance as a target for muscle modulation

Grade

Mantovani

Alvares

2019

J Animal Sci Biotechnol

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Myostatin (MSTN) is one of the key factors regulating myogenesis. Because of its role as a negative regulator of muscle mass deposition, much interest has been given to its protein and, in recent years, several studies have analysed MSTN gene regulation. This review discusses the MSTN gene promoter, focusing on its structure in several animal species, both vertebrate and invertebrate. We report the important binding sites considering their degree of phylogenetic conservation and roles they play in the promoter activity. Finally, we discuss recent studies focusing on MSTN gene regulation via promoter manipulation and the potential applications they have both in medicine and agriculture. Electronic supplementary material The online version of this article (10.1186/s40104-019-0338-5) contains supplementary material, which is available to authorized users.

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Structural and functional analysis of myostatin-2 promoter alleles from the marine fish Sparus aurata: Evidence for strong muscle-specific promoter activity and post-transcriptional regulation

Cited by 12 publications

References 67 publications

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides)

Myostatin gene promoter: structure, conservation and importance as a target for muscle modulation

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