title: Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory.
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.
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Barrett
authors.forename: Melissa
authors.initials: M
authors.lastname: Malvaez
authors.forename: Eniko
authors.initials: E
authors.lastname: Kramar
authors.forename: Dina P
authors.initials: DP
authors.lastname: Matheos
authors.forename: Abraham
authors.initials: A
authors.lastname: Arrizon
authors.forename: Sara M
authors.initials: SM
authors.lastname: Cabrera
authors.forename: Gary
authors.initials: G
authors.lastname: Lynch
authors.forename: Robert W
authors.initials: RW
authors.lastname: Greene
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000172:deficiency* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D006657:Histones; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse