Drug Discov Ther. 2021;15(2):55-65. (DOI: 10.5582/ddt.2021.01017)

Ezh1 regulates expression of Cpg15/Neuritin in mouse cortical neurons

Utsunomiya S, Kishi Y, Tsuboi M, Kawaguchi D, Gotoh Y, Abe M, Sakimura K, Maeda K,Takemoto H


Immature neurons undergo morphological and physiological maturation in order to establish neuronal networks. During neuronal maturation, a large number of genes change their transcriptional levels, and these changes may be mediated by chromatin modifiers. In this study, we found that the level of Ezh1, a component of Polycomb repressive complex 2 (PRC2), increases during neuronal maturation in mouse neocortical culture. In addition, conditional knockout of Ezh1 in post-mitotic excitatory neurons leads to downregulation of a set of genes related to neuronal maturation. Moreover, the locus encoding Cpg15/Neuritin (Nrn1), which is regulated by neuronal activity and implicated in stabilization and maturation of excitatory synapses, is a direct target of Ezh1 in cortical neurons. Together, these results suggest that elevated expression of Ezh1 contributes to maturation of cortical neurons.

KEYWORDS: epigenetics, Polycomb group proteins, neuronal maturation, depression, Alzheimer's disease, Nrn1

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