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http://purl.uniprot.org/citations/21884692http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21884692http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21884692http://www.w3.org/2000/01/rdf-schema#comment"Adult skeletal muscles in vertebrates are composed of different types of myofibers endowed with distinct metabolic and contraction speed properties. Genesis of this fiber-type heterogeneity during development remains poorly known, at least in mammals. Six1 and Six4 homeoproteins of the Six/sine oculis family are expressed throughout muscle development in mice, and Six1 protein is enriched in the nuclei of adult fast-twitch myofibers. Furthermore, Six1/Six4 proteins are known to control the early activation of fast-type muscle genes in myocytes present in the mouse somitic myotome. Using double Six1:Six4 mutants (SixdKO) to dissect in vivo the genesis of muscle fiber-type heterogeneity, we analyzed here the phenotype of the dorsal/epaxial muscles remaining in SixdKO. We show by electron microscopy analysis that the absence of these homeoproteins precludes normal sarcomeric organization of the myofiber leading to a dystrophic aspect, and by immunohistochemistry experiments a deficiency in synaptogenesis. Affymetrix transcriptome analysis of the muscles remaining in E18.5 SixdKO identifies a major role for these homeoproteins in the control of genes that are specifically activated in the adult fast/glycolytic myofibers, particularly those controlling Ca(2+) homeostasis. Absence of Six1 and Six4 leads to the development of dorsal myofibers lacking expression of fast-type muscle genes, and mainly expressing a slow-type muscle program. The absence of restriction of the slow-type program during the fetal period in SixdKO back muscles is associated with a decreased HDAC4 protein level, and subcellular relocalization of the transcription repressor Sox6. Six genes thus behave as essential global regulators of muscle gene expression, as well as a central switch to drive the skeletal muscle fast phenotype during fetal development."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.org/dc/terms/identifier"doi:10.1016/j.ydbio.2011.08.010"xsd:string
http://purl.uniprot.org/citations/21884692http://purl.org/dc/terms/identifier"doi:10.1016/j.ydbio.2011.08.010"xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Huang R."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Huang R."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Schmitt A."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Schmitt A."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Legay C."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Legay C."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Sakakibara I."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Sakakibara I."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Cagnard N."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Cagnard N."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Maire P."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Maire P."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Demignon J."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Demignon J."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Favier M."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Favier M."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Le Grand F."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Le Grand F."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Sgarioto N."xsd:string
http://purl.uniprot.org/citations/21884692http://purl.uniprot.org/core/author"Sgarioto N."xsd:string