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The Role of the Chromatin Modifying Enzymes CBP and HDAC3 in Long-term Memory Processes

出版	University of California, Irvine, 2011
ISBN	11248808799781124880877
URL	http://books.google.com.hk/books?id=au-HAQAACAAJ&hl=&source=gbs_api

註釋It has long been appreciated that the expression of specific genes is required for long-term memory storage, but the molecular mechanisms responsible for the regulation of transcription during memory consolidation remain the subject of intense investigation. Recently, several studies have demonstrated a pivotal role for the histone acetylation in memory and synaptic plasticity. Therefore, this dissertation focuses on the role of chromatin modifying enzymes, specifically CBP and HDAC3, in regulating gene expression in the hippocampus, a brain region involved in spatial and contextual memory, during long-term memory formation. I show here, using genetic and pharmacological methods, that CBP and HDAC3 have critical roles in the hippocampus in acetylating specific histone residues, regulating activity-dependent gene expression, and long-term memory formation. Further, I demonstrate that the effect of a loss of CBP cannot be compensated for by the inhibition of HDACs and that immediate early gene Nr4a2 is necessary for the enhancement of memory by HDAC3 inhibition. Together my results indicate a role for the balance of histone acetylation and deacetylation during long-term memory formation, specifically carried out by CBP and HDAC3.