Gene silencing by S-adenosylmethionine in muscle differentiation.
A well-characterised experimental system, the myogenin gene in C2C12 muscle cell culture, was chosen to better understand the methylation mechanism underlying the regulation of gene expression. We already demonstrated that demethylation dynamics of a specific CpG site in the 5'-flanking region of myogenin well correlates with gene expression and terminal differentiation. Here we demonstrate that S-adenosylmethionine-sulphate-p-toluenesulphonate (SAM) inhibits myogenin expression and myoblast differentiation by delaying the demethylation of specific CpG in differentiating myoblasts. These results suggest new perspectives in methylation mechanisms and the use of SAM in the partial silencing of gene expression, as it could be required in disease treatment.
Fuso
A
A
Department of Cellular Biotechnologies and Hematology, Research Laboratory, Rome, Italy.
Cavallaro
R A
RA
Orrù
L
L
Buttarelli
F R
FR
Scarpa
S
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D051796:Inhibitor of Differentiation Proteins; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018008:Myogenin / Q000235:genetics*; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D003470:Culture Media; D051796:Inhibitor of Differentiation Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D009363:Neoplasm Proteins; D014157:Transcription Factors; C075640:ID3 protein, human; D012436:S-Adenosylmethionine