Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory
Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory
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DOI：
10.1038/npp.2011.61
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发表时间：
2011-07-01
影响因子：
7.6
通讯作者：
Wood, Marcelo A.
中科院分区：
文献类型：
--
作者：
Barrett, Ruth M.;Malvaez, Melissa;Wood, Marcelo A.
为了确定组蛋白乙酰转移酶（HAT）CREB结合蛋白（CBP）在记忆形成过程中海马CA 1区神经元中的作用，我们研究了局灶性纯合敲除CBP对组蛋白修饰、基因表达、突触可塑性和长期记忆的影响。我们发现CBP对组蛋白H2 B、H3和H4上赖氨酸的体内乙酰化至关重要。CBP的同源物p300不能补偿CBP的损失。缺乏CBP的神经元维持转录因子CREB的磷酸化，但未能激活CREB：CBP介导的基因表达。海马背侧CA 1区CBP的缺失导致对情境恐惧和物体识别的长时程增强和长时程记忆的选择性损害。总之，这些结果表明，特定的染色质修饰的必要作用，选择性介导的CBP在巩固记忆。Neuropsychopharmacology（2011）36，1545-1556; doi：10.1038/npp.2011.61; 2011年4月20日在线发表
To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB: CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. Neuropsychopharmacology (2011) 36, 1545-1556; doi:10.1038/npp.2011.61; published online 20 April 2011