RESUMO
Myogenesis is inhibited by receptor activation of Ras through the MEK and ERK kinases, but the underlying mechanism is unclear. In this issue of Molecular Cell, Perry et al. show that activated MEK1 forms an inhibitory complex with myogenic transcription factors in the nucleus.
Assuntos
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Músculo Esquelético/fisiologia , Proteína MyoD/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Diferenciação Celular , Regulação da Expressão Gênica no Desenvolvimento , MAP Quinase Quinase 1 , Sistema de Sinalização das MAP Quinases , Desenvolvimento Muscular , Músculo Esquelético/citologia , Músculo Esquelético/crescimento & desenvolvimentoRESUMO
An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.
