SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression

Abstract

Methyl-CpG binding protein 2 (MeCP 2) binds methylated cytosines at CpG sites on DNA and it is thought to function as a critical epigenetic regulator. Mutations in the MeCP2 gene have been associated to Rett syndrome, a human neurodevelopmental disorder. Here we show that MeCP 2 is acetylated by p300 and that SIRT1 mediates its deacetylation. SIRT1, the mammalian homologue of Sir2 in yeast, is a nicotinamide-adenine dinucleotide (NAD+)-dependent histone deacetylase that belongs to the family of HDAC class III sirtuins. Importantly, SIRT1 has been shown to play a critical role in synaptic plasticity and memory formation. This study reveals a functional interplay between two critical epigenetic regulators, MeCP 2 and SIRT1, which controls MeCP 2 binding activity to the brain-derived neurotrophic factor (BDNF) promoter in a specific region of the brain. © 2012 Landes Bioscience.