SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression

 Abstract

Methyl-CpG binding protein 2 (MeCP2) 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 MeCP2 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, MeCP2 and SIRT1, which controls MeCP2 binding activity to the brain-derived neurotrophic factor (BDNF) promoter in a specific region of the brain.

Full Text Options
Article
Metrics
 Share
 Full Text
 Supplemental Material
 Info
Pages
695 - 700
doi
10.4161/epi.20733
Type
Research Paper
 Metrics
 Cite This Article
 Permissions
Creative Commons License Permissions
 Reprints
SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression