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Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element

Brown, David M.; Brameld, John M.; Parr, Tim

Authors

David M. Brown

JOHN BRAMELD JOHN.BRAMELD@NOTTINGHAM.AC.UK
Professor of Nutritional Biochemstry

TIM PARR tim.parr@nottingham.ac.uk
Professor of Nutritional Biochemistry



Abstract

Due to its similarity to humans, the pig is increasingly being considered as a good animal model for studying a range of human diseases. Despite their physiological similarities, differential expression of the myosin heavy chain (MyHC) IIB gene (MYH4) exists in the skeletal muscles of these species, which is associated with a different muscle phenotype. The expression of different MyHC isoforms is a critical determinant of the contractile and metabolic characteristics of the muscle fibre. We aimed to elucidate whether a genomic mechanism was responsible for the drastically different expression of MYH4 between pigs and humans, thus improving our understanding of the pig as a model for human skeletal muscle research. We utilized approximately 1 kb of the MYH4 promoter from a domestic pig and a human (which do and do not express MYH4, respectively) to elucidate the role of the promoter sequence in regulating the high expression of MYH4 in porcine skeletal muscle. We identified a 3 bp genomic difference within the proximal CArG and Ebox region of the MYH4 promoter of pigs and humans that dictates the differential activity of these promoters during myogenesis. Subtle species-specific genomic differences within the CArG-box region caused differential protein-DNA interactions at this site and is likely accountable for the differential MYH4 promoter activity between pigs and humans. We propose that the genomic differences identified herein explain the differential activity of the MYH4 promoter of pigs and humans, which may contribute to the differential expression patterns displayed in these otherwise physiologically similar mammals. Further, we report that both the pig and human MYH4 promoters can be induced by MyoD over- expression, but the capacity to activate the MYH4 promoter is largely influenced by the 3 bp difference located within the CArG-box region of the proximal MYH4 promoter.

Journal Article Type Article
Publication Date Dec 3, 2014
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 12
Article Number e114365
APA6 Citation Brown, D. M., Brameld, J. M., & Parr, T. (2014). Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element. PLoS ONE, 9(12), https://doi.org/10.1371/journal.pone.0114365
DOI https://doi.org/10.1371/journal.pone.0114365
Publisher URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114365
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Additional Information Brown DM, Brameld JM, Parr T (2014) Expression of the Myosin Heavy Chain IIB Gene in Porcine Skeletal Muscle: The Role of the CArG-Box Promoter Response Element. PLoS
ONE 9(12): e114365. doi:10.1371/journal.pone.0114365

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MyHC IIB paper (Brown et al, 2014).pdf (1.5 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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