The role of Sir2alpha in myogenesis

Title: The role of Sir2alpha in myogenesis
Authors: Abrol, Meena
Date: 2003
Abstract: Protein acetylation is becoming recognized as an important modification in the regulation of many cellular pathways. The silent information regulator 2 (Sir2) proteins are a family of NAD-dependent protein deacetylases. Sir2 protein function in yeast has extensively been characterized as an essential mediator of gene silencing that occurs at the mating type loci, the telomeres and the rDNA regions. There are Sir2 homologues from yeast to mammals, but little is known about the role of Sir2 in the mammalian system. There is evidence that myogenesis is regulated by the acetylation state of the histones in the promoter region of muscle-specific genes as well as the myogenic transcription factors. MyoD is a myogenic transcription factor that plays a key role in myogenesis. Its activity is required to initiate and maintain transcription of muscle-specific genes. In addition to this, acetylation of MyoD is required for its activity. We set out to determine if MyoD is a target for deacetylation by Sir2alpha, and thus determine if Sir2alpha has a role in myogenesis. We determined that MyoD transactivation activity is not inhibited by Sir2alpha deacetylation. Over-expression of Sir2alpha-wt or a catalytically inactive mutant Sir2alpha-H355Y in C2C12 cells also showed that Sir2alpha deacetylase activity does not effect myogenesis. In addition to this, nicotinamide, a Sir2 inhibitor, had no effect on myogenesis while TSA significantly inhibited myogenesis in the C2C12 cells, suggesting that Class I and II HDACs have a more important role than Sir2 in regulating MyoD activity.
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
MQ90018.PDF3.49 MBAdobe PDFOpen