An Evolutionarily Conserved Myostatin Proximal Promoter/enhancer Confers Basal Levels Of Transcription And Spatial Specificity In Vivo.

dc.creatorGrade, Carla Vermeulen Carvalho
dc.creatorSalerno, Mônica Senna
dc.creatorSchubert, Frank R
dc.creatorDietrich, Susanne
dc.creatorAlvares, Lúcia Elvira
dc.date2009-Oct
dc.date2015-11-27T13:18:39Z
dc.date2015-11-27T13:18:39Z
dc.date.accessioned2018-03-29T01:12:22Z
dc.date.available2018-03-29T01:12:22Z
dc.identifierDevelopment Genes And Evolution. v. 219, n. 9-10, p. 497-508, 2009-Oct.
dc.identifier1432-041X
dc.identifier10.1007/s00427-009-0312-x
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/20052486
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/199234
dc.identifier20052486
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1299467
dc.descriptionMyostatin (Mstn) is a negative regulator of skeletal muscle mass, and Mstn mutations are responsible for the double muscling phenotype observed in many animal species. Moreover, Mstn is a positive regulator of adult muscle stem cell (satellite cell) quiescence, and hence, Mstn is being targeted in therapeutic approaches to muscle diseases. In order to better understand the mechanisms underlying Mstn regulation, we searched for the gene's proximal enhancer and promoter elements, using an evolutionary approach. We identified a 260-bp-long, evolutionary conserved region upstream of tetrapod Mstn and teleost mstn b genes. This region contains binding sites for TATA binding protein, Meis1, NF-Y, and for CREB family members, suggesting the involvement of cAMP in Myostatin regulation. The conserved fragment was able to drive reporter gene expression in C2C12 cells in vitro and in chicken somites in vivo; both normally express Mstn. In contrast, the reporter construct remained silent in the avian neural tube that normally does not express Mstn. This suggests that the identified element serves as a minimal promoter, harboring some spatial specificity. Finally, using bioinformatic approaches, we identified additional genes in the human genome associated with sequences similar to the Mstn proximal promoter/enhancer. Among them are genes important for myogenesis. This suggests that Mstn and these genes may form a synexpression group, regulated by a common signaling pathway.
dc.description219
dc.description497-508
dc.languageeng
dc.relationDevelopment Genes And Evolution
dc.relationDev. Genes Evol.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectEnhancer Elements, Genetic
dc.subjectHumans
dc.subjectMolecular Sequence Data
dc.subjectMyostatin
dc.subjectPromoter Regions, Genetic
dc.subjectTranscription, Genetic
dc.titleAn Evolutionarily Conserved Myostatin Proximal Promoter/enhancer Confers Basal Levels Of Transcription And Spatial Specificity In Vivo.
dc.typeArtículos de revistas


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