Abstract：
:In the brain, enormous numbers of neurons have functional individuality and distinct circuit specificities. Clustered Protocadherins (Pcdhs), diversified cell-surface proteins, are stochastically expressed by alternative promoter choice and affect dendritic arborization in individual neurons. Here we found that the Pcdh promoters are differentially methylated by the de novo DNA methyltransferase Dnmt3b during early embryogenesis. To determine this methylation's role in neurons, we produced chimeric mice from Dnmt3b-deficient induced pluripotent stem cells (iPSCs). Single-cell expression analysis revealed that individual Dnmt3b-deficient Purkinje cells expressed increased numbers of Pcdh isoforms; in vivo, they exhibited abnormal dendritic arborization. These results indicate that DNA methylation by Dnmt3b at early embryonic stages regulates the probability of expression for the stochastically expressed Pcdh isoforms. They also suggest a mechanism for a rare human recessive disease, the ICF (Immunodeficiency, Centromere instability, and Facial anomalies) syndrome, which is caused by Dnmt3b mutations.
journal_name
Neuronjournal_title
Neuronauthors
Toyoda S,Kawaguchi M,Kobayashi T,Tarusawa E,Toyama T,Okano M,Oda M,Nakauchi H,Yoshimura Y,Sanbo M,Hirabayashi M,Hirayama T,Hirabayashi T,Yagi Tdoi
10.1016/j.neuron.2014.02.005subject
Has Abstractpub_date
2014-04-02 00:00:00pages
94-108issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(14)00103-2journal_volume
82pub_type
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