DNA甲基化和神经可塑性.pdf

Available online at Neurobiology of Learning and Memory 89 (2008) 599–603 /locate/ynlme Brief Report DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity Courtney A. Miller *, Susan L. Campbell, J. David Sweatt Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1074 Shelby Building, 1825 University Boulevard, Birmingham, USA Received 14 June 2007; revised 18 July 2007; accepted 23 July 2007 Available online 18 September 2007 Abstract A clear understanding is developing concerning the importance of epigenetic-related molecular mechanisms in transcription-depen- dent long-term memory formation. Chromatin modi?cation, in particular histone acetylation, is associated with transcriptional activa- tion, and acetylation of histone 3 (H3) occurs in Area CA1 of the hippocampus following contextual fear conditioning training. Conversely, DNA methylation is associated with transcriptional repression, but is also dynamically regulated in Area CA1 following training. We recently reported that inhibition of the enzyme responsible for DNA methylation, DNA methyltransferase (DNMT), in the adult rat hippocampus blocks behavioral memory formation. Here, we report that DNMT inhibition also blocks the concomitant memory-associated H3 acetylation, without a?ecting phosphorylation of its upstream regulator, extracellular signal-regulated kinase (ERK). Interestingly, the DNMT inhibitor-induced de?cit in memory consolidation, along with de?cits in long-term potentiation, can be rescued by pharmacologically i