title: Co-operation between enhancers modulates quantitative expression from the Drosophila Paramyosin/miniparamyosin gene in different muscle types.
abstract: The distinct muscles of an organism accumulate different quantities of structural proteins, but always maintaining their stoichiometry. However, the mechanisms that control the levels of these proteins and that co-ordinate muscle gene expression remain to be defined. The paramyosin/miniparamyosin gene encodes two thick filament proteins transcribed from two different promoters. We have analysed the regulatory regions that control expression of this gene and that are situated in the two promoters, the 5' and the internal promoters, both in vivo and in silico. A distal muscle enhancer containing three conserved MEF2 motifs is essential to drive high levels of paramyosin expression in all the major embryonic, larval and adult muscles. This enhancer shares sequence motifs, as well as its structure and organisation, with at least four co-regulated muscle enhancers that direct similar patterns of expression. However, other elements located downstream of the enhancer are also required for correct gene expression. Other muscle genes with different patterns of expression, such as miniparamyosin, are regulated by other basic mechanisms. The expression of miniparamyosin is controlled by two enhancers, AB and TX, but a BF modulator is required to ensure the correct levels of expression in each particular muscle. We propose a mechanism of transcriptional regulation in which similar enhancers are responsible for the spatio-temporal expression of co-regulated genes. However, it is the interaction between enhancers which ensures that the correct amounts of protein are expressed at any particular time in a cell, adapting these levels to their specific needs. These mechanisms may not be exclusive to neural or muscle tissue and might represent a general mechanism for genes that are spatially and temporally co-regulated.
authors.affiliation: Departamento de Bioquímica and Instituto Investigaciones Biomédicas, Facultad de Medicina, UAM-CSIC, Arzobispo Morcillo 4, 28029 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Marco-Ferreres
authors.forename: Jorge
authors.initials: J
authors.lastname: Vivar
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Arredondo
authors.forename: Francisco
authors.initials: F
authors.lastname: Portillo
authors.forename: Margarita
authors.initials: M
authors.lastname: Cervera
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004331:Drosophila melanogaster; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D016678:Genome; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D019076:Transgenes; D014335:Tropomyosin / Q000096:biosynthesis / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D009711:Nucleotides; D014335:Tropomyosin; D001616:beta-Galactosidase