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

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,...

Full description

Bibliographic Details
Main Authors: Brown, David M., Brameld, John M., Parr, Tim
Format: Article
Published: Public Library of Science 2014
Online Access:https://eprints.nottingham.ac.uk/44881/
_version_ 1848797019510931456
author Brown, David M.
Brameld, John M.
Parr, Tim
author_facet Brown, David M.
Brameld, John M.
Parr, Tim
author_sort Brown, David M.
building Nottingham Research Data Repository
collection Online Access
description 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.
first_indexed 2025-11-14T19:57:13Z
format Article
id nottingham-44881
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T19:57:13Z
publishDate 2014
publisher Public Library of Science
recordtype eprints
repository_type Digital Repository
spelling nottingham-448812020-05-04T16:59:14Z https://eprints.nottingham.ac.uk/44881/ 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 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. Public Library of Science 2014-12-03 Article PeerReviewed Brown, David M., Brameld, John M. and Parr, Tim (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). e114365/1-e114365/17. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114365 doi:10.1371/journal.pone.0114365 doi:10.1371/journal.pone.0114365
spellingShingle Brown, David M.
Brameld, John M.
Parr, Tim
Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title_full Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title_fullStr Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title_full_unstemmed Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title_short Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
title_sort expression of the myosin heavy chain iib gene in porcine skeletal muscle: the role of the carg-box promoter response element
url https://eprints.nottingham.ac.uk/44881/
https://eprints.nottingham.ac.uk/44881/
https://eprints.nottingham.ac.uk/44881/