Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis.
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.
Ma
Dengke K
DK
Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA. dma2@jhmi.edu
Jang
Mi-Hyeon
MH
Guo
Junjie U
JU
Kitabatake
Yasuji
Y
Chang
Min-Lin
ML
Pow-Anpongkul
Nattapol
N
Flavell
Richard A
RA
Lu
Binfeng
B
Ming
Guo-Li
GL
Song
Hongjun
H
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D004597:Electroshock; D044127:Epigenesis, Genetic; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D020869:Gene Expression Profiling; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D005082:Physical Exertion; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D015533:Transcriptional Activation; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D004247:DNA; D016220:Fibroblast Growth Factor 1; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins