The role of the de novo DNA methyltransferase Dnmt3a in the nervous system

Abstract

DNA methylation is an important mechanism of gene regulation. Evidence is mounting that epigenetic mechanisms including that of DNA methylation operate in the nervous system. Genetic disruption of the de novo DNA methyltransferase Dnmt3a in mice were used to elucidate the role of the enzyme in the nervous system. Inactivating Dnmt3a in the nervous system resulted in a drastically shortened lifespan and in behavioral abnormalities that suggested a motor defect. Dnmt3a mutants also exhibited motor neuron loss and fragmented neuromuscular junction synapses. These results support a requirement for DNA methyltransferase activity in the neuromuscular system.