Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis (Science, 2009, doi:10.1126/science.1166859)

報告日期: 2009/05/01
報告時間: 15:10/16:00
報告學生: 趙詠梅
講評老師: 黃阿敏

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


Dengke K. Ma, Mi-Hyeon Jang, Junjie U. Guo, Yasuji Kitabatake, Min-lin Chang, Nattapol Pow-anpongkul, Richard A. Flavell, Binfeng Lu, Guo-li Ming, Hongjun Song

Science, 2009, 323:1074-1077


Speaker: 趙詠梅

Commentator: Dr. 黃阿敏

Time: 2009/05/01 pm 3:10~4:00

Place: R602



    Neurogenesis in the adult mammalian brain involves activity-dependent expression of genes critical for the proliferation of progenitors and for neuronal maturation. In most mammals, active neurogenesis occurs throughout life in the subventricular zone (SVZ) of the lateral ventricle and in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. Adult neurogenesis is modulated by a surplus of external stimuli, but how transient activation of mature neurons modulates adult neurogenesis over days and weeks is largely unknown. Here the authors identify the stress response gene Gadd45b (growth arrest and DNA-damage-inducible protein 45 beta) as a neural activity-induced immediate early gene in mature hippocampal neurons. This study suggests that Gadd45b can be transiently induced by neuronal activity and promotes adult neurogenesis through dynamic DNA demethylation of specific gene promoters, including brain-derived neurotrophic factor (Bdnf) and fibroblast growth factor-1 (Fgf-1), in adult hippocampus. Gadd45b links neuronal activity to region-specific DNA methylation and expression of paracrine neurogenic niche factors from mature neurons for extrinsic modulation of adult neurogenesis. Results reported in this study provide evidence supporting the provocative ideas that active DNA demethylation may occur in postmitotic neurons and that epigenetic DNA modification is involved in regulating long-lasting changes in neural plasticity in mammalian brains.



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2.   Wu H. and Sun YE. (2009) Reversing DNA Methylation: New Insights from Neuronal Activity Induced Gadd46b in Adult Neurogenesis. Sci. Signal. 2: 1-3.