An evolutionarily conserved Myostatin proximal promoter/enhancer confers basal levels of transcription and spatial specificity in vivo

Autor(es)

Carvalho Grade, Carla Vermeulen ^[1] ; Salerno, Monica Senna ^[2] ; Schubert, Frank R. ^[3] ; Dietrich, Susanne ^[4] ; Alvares, Lucia Elvira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Histol & Embryol, BR-13083863 Campinas, SP - Brazil

^[2] Funct Muscle Genom AgRes Ruakura Res Ctr, Hamilton - New Zealand

^[3] Univ Portsmouth, Sch Biol Sci, Inst Biomed & Biomol Sci, Portsmouth PO1 2DY, Hants - England

^[4] Kings Coll London, Sch Biomed & Hlth Sci, London SE1 1UL - England

• Tipo de documento: Artigo Científico
• Fonte: DEVELOPMENT GENES AND EVOLUTION; v. 219, n. 9-10, p. 497-508, OCT 2009.
• Citações Web of Science: 16

Resumo

Myostatin (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. (AU)

• Processo FAPESP: 06/05375-9 - Identificacao e caracterizacao funcional dos elementos cis-regulatorios da miostatina.
• Beneficiário: Carla Vermeulen Carvalho Grade
• Modalidade de apoio: Bolsas no Brasil - Mestrado