期刊
EMBO REPORTS
卷 20, 期 9, 页码 -出版社
WILEY
DOI: 10.15252/embr.201845907
关键词
CREB; hippocampus; learning and memory; lysine methylation; PHF2
资金
- National Research Foundation grants from the Korean government [2016R1AB4013377, 2018R1A2B6007241, 2018R1A5A2025964]
- BK21-plus education program by the National Research Foundation of Korea
- National Research Foundation of Korea [2018R1A2B6007241] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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