title: Spatial memory consolidation is associated with induction of several lysine-acetyltransferase (histone acetyltransferase) expression levels and H2B/H4 acetylation-dependent transcriptional events in the rat hippocampus.
abstract: Numerous genetic studies have shown that the CREB-binding protein (CBP) is an essential component of long-term memory formation, through its histone acetyltransferase (HAT) function. E1A-binding protein p300 and p300/CBP-associated factor (PCAF) have also recently been involved in memory formation. By contrast, only a few studies have reported on acetylation modifications during memory formation, and it remains unclear as to how the system is regulated during this dynamic phase. We investigated acetylation-dependent events and the expression profiles of these HATs during a hippocampus-dependent task taxing spatial reference memory in the Morris water maze. We found a specific increase in H2B and H4 acetylation in the rat dorsal hippocampus, while spatial memory was being consolidated. This increase correlated with the degree of specific acetylated histones enrichment on some memory/plasticity-related gene promoters. Overall, a global increase in HAT activity was measured during this memory consolidation phase, together with a global increase of CBP, p300, and PCAF expression. Interestingly, these regulations were altered in a model of hippocampal denervation disrupting spatial memory consolidation, making it impossible for the hippocampus to recruit the CBP pathway (CBP regulation and acetylated-H2B-dependent transcription). CBP has long been thought to be present in limited concentrations in the cells. These results show, for the first time, that CBP, p300, and PCAF are dynamically modulated during the establishment of a spatial memory and are likely to contribute to the induction of a specific epigenetic tagging of the genome for hippocampus-dependent (spatial) memory consolidation. These findings suggest the use of HAT-activating molecules in new therapeutic strategies of pathological aging, Alzheimer's disease, and other neurodegenerative disorders.
authors.affiliation: Inserm, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bousiges
authors.forename: Anne Pereira de
authors.initials: AP
authors.lastname: Vasconcelos
authors.forename: Romain
authors.initials: R
authors.lastname: Neidl
authors.forename: Brigitte
authors.initials: B
authors.lastname: Cosquer
authors.forename: Karine
authors.initials: K
authors.lastname: Herbeaux
authors.forename: Irina
authors.initials: I
authors.lastname: Panteleeva
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
authors.forename: Anne-Laurence
authors.initials: AL
authors.lastname: Boutillier
mesh_terms: D000107:Acetylation; D000818:Animals; D050882:CREB-Binding Protein / Q000096:biosynthesis; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000096:biosynthesis*; D006657:Histones / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013037:Spatial Behavior / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis; D000099224:p300-CBP-Associated Factor
chemical_list: D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D006657:Histones; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
references.citation: Nature. 2007 May 10;447(7141):178-82
references.pmid: 17468743
references.citation: J Neurosci. 2001 Jul 15;21(14):5089-98
references.pmid: 11438584
references.citation: Neuron. 2004 Jun 24;42(6):947-59
references.pmid: 15207239
references.citation: J Neurosci. 2007 May 23;27(21):5535-45
references.pmid: 17522299
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: Cell Death Differ. 2006 Apr;13(4):539-50
references.pmid: 16167067
references.citation: Learn Mem. 2007 Aug 29;14(9):564-72
references.pmid: 17761541
references.citation: Neuropsychopharmacology. 2007 Apr;32(4):851-71
references.pmid: 16760925
references.citation: J Neurosci Res. 2007 Feb 15;85(3):525-35
references.pmid: 17149751
references.citation: Learn Mem. 2006 May-Jun;13(3):241-4
references.pmid: 16741277
references.citation: Biol Psychiatry. 2009 Feb 1;65(3):191-7
references.pmid: 19006788
references.citation: J Cancer Res Clin Oncol. 2002 Mar;128(3):135-40
references.pmid: 11935299
references.citation: Am J Pathol. 2007 Apr;170(4):1200-9
references.pmid: 17392160
references.citation: Nucleic Acids Res. 1983 Mar 11;11(5):1475-89
references.pmid: 6828386
references.citation: Learn Mem. 2006 Sep-Oct;13(5):609-17
references.pmid: 16980541
references.citation: Annu Rev Biochem. 2001;70:81-120
references.pmid: 11395403
references.citation: Neuron. 2007 Jan 18;53(2):261-77
references.pmid: 17224407
references.citation: Learn Mem. 2008 Jan 03;15(1):39-45
references.pmid: 18174372
references.citation: J Neuropathol Exp Neurol. 2009 Dec;68(12):1282-93
references.pmid: 19915487
references.citation: Neuron. 1998 Apr;20(4):727-40
references.pmid: 9581764
references.citation: Learn Mem. 2007 Apr 06;14(4):268-76
references.pmid: 17522015
references.citation: Neuron. 2004 Jun 24;42(6):961-72
references.pmid: 15207240
references.citation: J Neurosci. 2010 Mar 10;30(10):3589-99
references.pmid: 20219993
references.citation: EMBO J. 2003 Dec 15;22(24):6537-49
references.pmid: 14657026
references.citation: Biochem Biophys Res Commun. 1995 May 16;210(2):409-16
references.pmid: 7755616
references.citation: Science. 2000 Jan 14;287(5451):248-51
references.pmid: 10634773
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9447-52
references.pmid: 19470462
references.citation: Cellscience. 2009 Jul 27;6(1):44-48
references.pmid: 19777123
references.citation: J Biol Chem. 2004 Sep 24;279(39):40545-59
references.pmid: 15273246
references.citation: Neuroscience. 2009 Sep 29;163(1):1-8
references.pmid: 19531374
references.citation: Neuropsychopharmacology. 2009 Jun;34(7):1721-32
references.pmid: 19145227
references.citation: Mol Cancer Res. 2007 Oct;5(10):981-9
references.pmid: 17951399
references.citation: Blood. 1999 May 1;93(9):2771-9
references.pmid: 10216070
references.citation: Behav Neurosci. 2007 Oct;121(5):1125-31
references.pmid: 17907845
references.citation: Am J Pathol. 2004 Aug;165(2):523-31
references.pmid: 15277226
references.citation: J Neurosci. 2008 Oct 15;28(42):10576-86
references.pmid: 18923034
references.citation: EMBO J. 2007 Aug 8;26(15):3616-28
references.pmid: 17627279
references.citation: Annu Rev Psychol. 2004;55:51-86
references.pmid: 14744210
references.citation: J Neurosci. 2007 Jun 6;27(23):6128-40
references.pmid: 17553985
references.citation: Prog Neurobiol. 2010 Apr;90(4):498-510
references.pmid: 20097254
references.citation: Nature. 2009 May 7;459(7243):55-60
references.pmid: 19424149
references.citation: Eur J Neurosci. 2009 Jul;30(1):1-8
references.pmid: 19508697
references.citation: Neuropsychopharmacology. 2010 Mar;35(4):870-80
references.pmid: 20010553
references.citation: Mol Cell Biol. 2006 May;26(10):3842-52
references.pmid: 16648479
references.citation: Learn Mem. 2005 Mar-Apr;12(2):111-9
references.pmid: 15805310
references.citation: Science. 2001 Nov 2;294(5544):1030-8
references.pmid: 11691980
references.citation: Behav Brain Res. 2008 Sep 1;192(1):70-87
references.pmid: 18353453
references.citation: Nano Lett. 2008 Oct;8(10):3182-8
references.pmid: 18800851
references.citation: J Pathol. 2004 Oct;204(2):159-66
references.pmid: 15378487
references.citation: J Alzheimers Dis. 2009;18(1):131-9
references.pmid: 19625751
references.citation: Curr Opin Neurobiol. 2009 Jun;19(3):336-42
references.pmid: 19539459
references.citation: Learn Mem. 2008 Jun 26;15(7):460-7
references.pmid: 18583646
references.citation: Nat Rev Neurosci. 2005 Feb;6(2):119-30
references.pmid: 15685217
references.citation: Behav Brain Res. 2008 Sep 1;192(1):61-9
references.pmid: 18374993
references.citation: Cell. 2007 Nov 16;131(4):633-6
references.pmid: 18022353
references.citation: J Immunol. 2009 Aug 1;183(3):2068-78
references.pmid: 19596989
references.citation: Biochem Pharmacol. 2004 Sep 15;68(6):1157-64
references.pmid: 15313413
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10518-22
references.pmid: 12930888
references.citation: J Neurosci. 2000 Jun 15;20(12):4563-72
references.pmid: 10844026
references.citation: Neuroscience. 2010 May 5;167(2):354-60
references.pmid: 20167251
references.citation: Biochim Biophys Acta. 2009 Jan;1789(1):37-44
references.pmid: 18675384
references.citation: J Biol Chem. 2001 Apr 27;276(17):13505-8
references.pmid: 11279224
references.citation: Neuropsychopharmacology. 2008 Jun;33(7):1584-602
references.pmid: 17805310
references.citation: Neurodegener Dis. 2008;5(5):304-17
references.pmid: 18520165
references.citation: Cell. 2004 Dec 29;119(7):1041-54
references.pmid: 15620361
references.citation: Nature. 1995 Jul 27;376(6538):348-51
references.pmid: 7630403