Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency.

ABSTRACT: The efficiency of remyelination decreases with age, but the molecular mechanisms responsible for this decline remain only partially understood. In this study, we show that remyelination is regulated by age-dependent epigenetic control of gene expression. In demyelinated young brains, new myelin synthesis is preceded by downregulation of oligodendrocyte differentiation inhibitors and neural stem cell markers, and this is associated with recruitment of histone deacetylases (HDACs) to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient, and this allows the accumulation of transcriptional inhibitors and prevents the subsequent surge in myelin gene expression. Defective remyelination can be recapitulated in vivo in mice receiving systemic administration of pharmacologi

SUBMITTER: Shen S 

PROVIDER: S-EPMC2656679 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature