逆转DNA甲基化：成年神经发生中神经元活动诱导的Gadd45b带来的新见解。

Reversing DNA methylation: new insights from neuronal activity-induced Gadd45b in adult neurogenesis.

作者信息

Wu Hao, Sun Yi Eve

机构信息

Department of Molecular and Medical Pharmacology, MRRC at University of California Los Angeles (UCLA) Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.

出版信息

Sci Signal. 2009 Mar 31;2(64):pe17. doi: 10.1126/scisignal.264pe17.

DOI:10.1126/scisignal.264pe17

PMID:19336837

Abstract

Neurogenesis in the adult mammalian brain involves activity-dependent expression of genes critical for the proliferation of progenitors and for neuronal maturation. A recent study suggests that the stress response gene Gadd45b (growth arrest and DNA-damage-inducible protein 45 beta) can be transiently induced by neuronal activity and may promote adult neurogenesis through dynamic DNA demethylation of specific gene promoters in adult hippocampus. These results provide evidence supporting the provocative ideas that active DNA demethylation may occur in postmitotic neurons and that DNA methylation-mediated dynamic epigenetic regulation is involved in regulating long-lasting changes in neural plasticity in mammalian brains.

摘要

成年哺乳动物大脑中的神经发生涉及对祖细胞增殖和神经元成熟至关重要的基因的活性依赖性表达。最近的一项研究表明，应激反应基因Gadd45b（生长停滞和DNA损伤诱导蛋白45β）可被神经元活动短暂诱导，并可能通过成年海马体中特定基因启动子的动态DNA去甲基化促进成年神经发生。这些结果为以下具有启发性的观点提供了证据支持：有丝分裂后神经元中可能发生活性DNA去甲基化，并且DNA甲基化介导的动态表观遗传调控参与调节哺乳动物大脑中神经可塑性的长期变化。