海马体特异性 CBP 缺失影响特定组蛋白修饰、长时程增强和长时记忆。
Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory.
机构信息
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800, USA.
出版信息
Neuropsychopharmacology. 2011 Jul;36(8):1545-56. doi: 10.1038/npp.2011.61. Epub 2011 Apr 20.
Abstract
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.
摘要
为了确定组蛋白乙酰转移酶（HAT）CREB 结合蛋白（CBP）在海马 CA1 区神经元中在记忆形成过程中的作用，我们研究了 CBP 纯合焦点敲除对组蛋白修饰、基因表达、突触可塑性和长期记忆的影响。我们表明 CBP 对于体内组蛋白 H2B、H3 和 H4 赖氨酸的乙酰化至关重要。CBP 的同源物 p300 无法弥补 CBP 的缺失。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 CA1 背侧的 CBP 缺失导致选择性损害了情景恐惧和物体识别的长时增强和长期记忆。总之，这些结果表明特定染色质修饰在记忆巩固中的特定作用，这是由 CBP 选择性介导的。
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