SIRT1 inhibition alleviates gene silencing in Fragile X mental retardation syndrome.

ABSTRACT: Expansion of the CGG.CCG-repeat tract in the 5' UTR of the FMR1 gene to >200 repeats leads to heterochromatinization of the promoter and gene silencing. This results in Fragile X syndrome (FXS), the most common heritable form of mental retardation. The mechanism of gene silencing is unknown. We report here that a Class III histone deacetylase, SIRT1, plays an important role in this silencing process and show that the inhibition of this enzyme produces significant gene reactivation. This contrasts with the much smaller effect of inhibitors like trichostatin A (TSA) that inhibit Class I, II and IV histone deacetylases. Reactivation of silenced FMR1 alleles was accompanied by an increase in histone H3 lysine 9 acetylation as well as an increase in the amount of histone H4 that is acetylated a

SUBMITTER: Biacsi R 

PROVIDER: S-EPMC2265469 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature