Neuronal Activity-Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis

被引：688

作者：

Ma, Dengke K. ^{[1
]}

Jang, Mi-Hyeon ^{[1
,2
]}

Guo, Junjie U. ^{[1
]}

Kitabatake, Yasuji ^{[1
,2
]}

Chang, Min-lin ^{[1
,2
]}

Pow-Anpongkul, Nattapol ^{[1
]}

Flavell, Richard A. ^{[3
]}

Lu, Binfeng ^{[4
]}

Ming, Guo-li ^{[1
,2
]}

Song, Hongjun ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[3] Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, New Haven, CT 06520 USA

[4] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15261 USA

来源：

SCIENCE | 2009年 / 323卷 / 5917期

关键词：

GENE-EXPRESSION; MESSENGER-RNA; MOUSE; TRANSCRIPTION; METHYLATION; MECHANISMS; PLASTICITY; SIGNALS; PROTEIN; CORTEX;

D O I：

10.1126/science.1166859

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The mammalian brain exhibits diverse types of neural plasticity, including activity- dependent neurogenesis in the adult hippocampus. How transient activation of mature neurons leads to long-lasting modulation of adult neurogenesis is unknown. Here we identify Gadd45b as a neural activity- induced immediate early gene in mature hippocampal neurons. Mice with Gadd45b deletion exhibit specific deficits in neural activity- induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus. Mechanistically, Gadd45b is required for activity- induced DNA demethylation of specific promoters and expression of corresponding genes critical for adult neurogenesis, including brain- derived neurotrophic factor and fibroblast growth factor. Thus, Gadd45b links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons for extrinsic modulation of neurogenesis in the adult brain.

引用

页码：1074 / 1077

页数：4

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