Dnmt1 and Dnmt3a two role players of synaptic function and methylation in Neurons

  Dnmt is an alternate name of DNA methyltransferase, and its function is commonly known as transferring a methyl group to DNA. Dnmt1 and Dnmt3a are two important and most abundant family members of DNA methyltransferase. Both Dnmt 1 and Dnmt3a are the key maintenance methyltransferase in human genome, and they usually prefer to methylate CpG in mammalian genome. Also, they plays an important role in DNA imprinting. From previous study, Dnmt1 and Dnmt3a have been considered as important factors of adaptive neuronal gene expression due to the epigenetic mechanisms. However, there is not any proofs or discoveries of these two factors would affect an adult nervous system. Thus, Fan et al. did a further study on how these two DNA methylation factors affect in adult forebrain neurons. The experiment used knockout mice as their research tool, and these knockout mice were divided into Dnmt1 single knockout, Dnmt3a single knockout, and double knockout. Then, they used the DKO mice to compare with two SKO and wild-type mice. As the results, a deficiency of both Dnmt1 and Dnmt3a would cause an unusual neuron size and neural plasticity; deficits in hippocampal learning and memory; upregulation of MHC I and other immune gene expression; Also, an abnormality on DNA methylation partterns in CNS neutrons. Therefore, overlapping of Dnmt1 and Dnmt3a is important for synaptic plasticity, learning and memory, and also maintaining DNA methylation partten in forebrain neurons. However, how these two DNA methyltransferases carry out overlapping function is unclear, but it is possible Dnmt1 and Dnmt3a could be co-operative during the DNA methylation in postmitotic neurons. Thus, a further study is essential for understanding of this regulation pathway.

Reference:

Guoping Fan,. Jiang Feng, et al. (2010). “Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons”. Nature Neuroscience 13:423-430.

Xiang Li

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