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EMBO Rep. 2019 Jul 30:e45907. doi: 10.15252/embr.201845907. [Epub ahead of print]

Histone demethylase PHF2 activates CREB and promotes memory consolidation.

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Department of Physiology and Biomedical Science, Seoul National University College of Medicine, Seoul, Korea.
Ischemic/Hypoxic disease Institutes, Seoul National University College of Medicine, Seoul, Korea.
Center for cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Korea.
Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.


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.


CREB; PHF2; hippocampus; learning and memory; lysine methylation


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