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Histone demethylase PHF2 activates CREB and promotes memory consolidation
- Source :
- EMBO Rep
- Publication Year :
- 2018
-
Abstract
- Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation are essential for the epigenetic regulation of memory consolidation-related genes. Here, we demonstrate that the plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during the experience phase and plays an essential role in memory formation. PHF2 promotes the expression of memory-related genes by epigenetically reinforcing the TrkB-CREB signaling pathway. In behavioral tests, memory formation is enhanced by transgenic overexpression of PHF2 in mice, but is impaired by silencing PHF2 in the hippocampus. Electrophysiological studies reveal that PHF2 elevates field excitatory postsynaptic potential (fEPSP) and NMDA receptor-mediated evoked excitatory postsynaptic current (EPSC) in CA1 pyramidal neurons, suggesting that PHF2 promotes long-term potentiation. This study provides insight into the epigenetic regulation of learning and memory formation, which advances our knowledge to improve memory in patients with degenerative brain diseases.
- Subjects :
- Male
Hippocampus
Mice, Transgenic
CREB
Biochemistry
Mass Spectrometry
Epigenesis, Genetic
03 medical and health sciences
Mice
0302 clinical medicine
Histone methylation
Genetics
Animals
Epigenetics
Maze Learning
Molecular Biology
030304 developmental biology
Memory Consolidation
Histone Demethylases
Homeodomain Proteins
0303 health sciences
biology
Computational Biology
Long-term potentiation
Articles
Cell biology
Mice, Inbred C57BL
nervous system
Excitatory postsynaptic potential
biology.protein
Demethylase
Memory consolidation
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14693178
- Volume :
- 20
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi.dedup.....1c391edd99ae01f70e83c578ef95444a