title: Muscle fiber type specific activation of the slow myosin heavy chain 2 promoter by a non-canonical E-box.
abstract: Different mechanisms control skeletal muscle fiber type gene expression at specific times in vertebrate development. Embryonic myogenesis leading to formation of primary muscle fibers in avian species is largely directed by myoblast cell commitment to the formation of diverse fiber types. In contrast, development of different secondary fiber types during fetal myogenesis is partly determined by neural influences. In both primary and secondary chicken muscle fibers, differential expression of the slow myosin heavy chain 2 (MyHC2) gene distinguishes fast from fast/slow muscle fibers. This study focused on the transcriptional regulation of the slow MyHC2 gene in primary myotubes formed from distinct fast/slow and fast myogenic cell lineages. Promoter deletion analyses identified a discrete 86 bp promoter segment that conferred fiber type, lineage-specific gene expression in fast/slow versus fast myoblast derived primary myotubes. Sequence analysis and promoter activity assays determined that this segment contains two functional cis-regulatory elements. One element is a non-canonical E-box, and electromobility shift assays demonstrated that both cis-elements interacted with the E-protein, E47. The results indicate that primary muscle fiber type specific expression of the slow MyHC2 gene is controlled by a novel mechanism involving a transcriptional complex that includes E47 at a non-canonical E-box.
authors.affiliation: School of Graduate and Postdoctoral Studies, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Weimer
authors.affiliation: School of Graduate and Postdoctoral Studies, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. Electronic address: joseph.dimario@rosalindfranklin.edu.
authors.forename: Joseph X
authors.initials: JX
authors.lastname: DiMario
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002645:Chickens; D024721:E-Box Elements / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D018006:Myogenic Regulatory Factors; D018995:Myosin Heavy Chains / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D018006:Myogenic Regulatory Factors; D018995:Myosin Heavy Chains
keywords: Embryonic; Gene regulation; Lineage; Myoblast; Myogenesis