Histone demethylase PHF2 activates CREB and promotes memory consolidation

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 u...

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Veröffentlicht in:EMBO reports 2019-09, Vol.20 (9), p.e45907-n/a
Hauptverfasser: Kim, Hye‐Jin, Hur, Sung Won, Park, Jun Bum, Seo, Jieun, Shin, Jae Jin, Kim, Seon‐Young, Kim, Myoung‐Hwan, Han, Do Hyun, Park, Jong‐Wan, Park, Joo Min, Kim, Sang Jeong, Chun, Yang‐Sook
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Sprache:eng
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Zusammenfassung: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. Synopsis Long‐term memory formation is established by experience‐dependent gene expression patterns. PHF2‐mediated epigenetic regulation of CREB serves as a molecular switch to link CREB‐dependent gene expression with activity‐dependent synaptic plasticity and memory. The PHF2 histone demethylase is upregulated after training and facilitates memory formation. PHF2 promotes long‐term potentiation in CA1 pyramidal neurons. PHF2 promotes the expression of memory‐related genes by epigenetically activating TrkB–CREB signaling. Graphical Abstract Long‐term memory formation is established by experience‐dependent gene expression patterns. PHF2‐mediated epigenetic regulation of CREB serves as a molecular switch to link CREB‐dependent gene expression with activity‐dependent synaptic plasticity and memory.
ISSN:1469-221X
1469-3178
1469-3178
DOI:10.15252/embr.201845907