CBP histone acetyltransferase activity is a critical component of memory consolidation.
The stabilization of learned information into long-term memories requires new gene expression. CREB binding protein (CBP) is a coactivator of transcription that can be independently regulated in neurons. CBP functions both as a platform for recruiting other required components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. To dissect the chromatin remodeling versus platform function of CBP or the developmental versus adult role of this gene, we generated transgenic mice that express CBP in which HAT activity is eliminated. Acquisition of new information and short-term memory is spared in these mice, while the stabilization of short-term memory into long-term memory is impaired. The behavioral phenotype is due to an acute requirement for CBP HAT activity in the adult as it is rescued by both suppression of transgene expression or by administration of the histone deacetylase inhibitor Trichostatin A (TSA) in adult animals.
Korzus
Edward
E
Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive 0986, La Jolla, CA 92093, USA. ekorzus@ucsd.edu
Rosenfeld
Michael G
MG
Mayford
Mark
M
D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D050882:CREB-Binding Protein; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D016762:Genes, fos / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D051548:Histone Acetyltransferases; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D015534:Trans-Activators; C012589:trichostatin A; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051548:Histone Acetyltransferases