title: Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction.
abstract: Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences, and Medical Scientist Training Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Risheng
authors.initials: R
authors.lastname: Xu
authors.forename: Bindu D
authors.initials: BD
authors.lastname: Paul
authors.forename: Dani R
authors.initials: DR
authors.lastname: Smith
authors.forename: Richa
authors.initials: R
authors.lastname: Tyagi
authors.forename: Feng
authors.initials: F
authors.lastname: Rao
authors.forename: A Basit
authors.initials: AB
authors.lastname: Khan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Blech
authors.forename: M Scott
authors.initials: MS
authors.lastname: Vandiver
authors.forename: Maged M
authors.initials: MM
authors.lastname: Harraz
authors.forename: Prasun
authors.initials: P
authors.lastname: Guha
authors.forename: Ishrat
authors.initials: I
authors.lastname: Ahmed
authors.forename: Nilkantha
authors.initials: N
authors.lastname: Sen
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D050882:CREB-Binding Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase
keywords: inositol phosphates; learning
references.citation: J Biol Chem. 2002 Nov 8;277(45):42711-8
references.pmid: 12226109
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22687-92
references.pmid: 21149712
references.citation: Nature. 1989 Aug 10;340(6233):474-6
references.pmid: 2547165
references.citation: Cell Cycle. 2013 Jun 15;12(12):1819-20
references.pmid: 23708509
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12783-8
references.pmid: 16123124
references.citation: Cell Metab. 2011 Feb 2;13(2):215-21
references.pmid: 21284988
references.citation: J Biol Chem. 2012 Nov 2;287(45):38347-55
references.pmid: 22992733
references.citation: Hum Mol Genet. 2012 Mar 15;21(6):1203-16
references.pmid: 22116937
references.citation: Science. 2011 Dec 23;334(6063):1669-75
references.pmid: 22194569
references.citation: Science. 2003 Jan 3;299(5603):114-6
references.pmid: 12434012
references.citation: Curr Biol. 1999 Nov 18;9(22):1323-6
references.pmid: 10574768
references.citation: FEBS Lett. 2000 Dec 15;486(3):300-4
references.pmid: 11119723
references.citation: Sci Signal. 2013 Apr 02;6(269):ra22
references.pmid: 23550211
references.citation: Proc Natl Acad Sci U S A. 2011 May 10;108(19):7814-9
references.pmid: 21518915
references.citation: Neuron. 2004 Jun 24;42(6):947-59
references.pmid: 15207239
references.citation: Nat Neurosci. 2001 Mar;4(3):289-96
references.pmid: 11224546
references.citation: Nature. 1987 Aug 13-19;328(6131):632-4
references.pmid: 3112583
references.citation: Neuron. 2003 Nov 13;40(4):695-701
references.pmid: 14622575
references.citation: Mol Microbiol. 2003 Jul;49(2):457-68
references.pmid: 12828642
references.citation: Nature. 2012 Jan 09;481(7381):335-40
references.pmid: 22230954
references.citation: Neuron. 2011 Feb 10;69(3):437-44
references.pmid: 21315255
references.citation: Neuron. 2004 Jun 24;42(6):961-72
references.pmid: 15207240
references.citation: Neuron. 2006 Nov 9;52(3):437-44
references.pmid: 17088210
references.citation: Biotechniques. 2005 Nov;39(5):715-25
references.pmid: 16315372
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8454-9
references.pmid: 15939867
references.citation: Neuron. 1995 Apr;14(4):813-23
references.pmid: 7718243
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5764-8
references.pmid: 1631058
references.citation: Genes Dev. 2001 Apr 1;15(7):859-76
references.pmid: 11297510
references.citation: Genes Dev. 2000 Jul 1;14(13):1553-77
references.pmid: 10887150
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1391-6
references.pmid: 21220345
references.citation: J Biol Chem. 2012 Oct 12;287(42):35360-35369
references.pmid: 22896696
references.citation: Science. 2000 Mar 17;287(5460):2026-9
references.pmid: 10720331
references.citation: Nat Genet. 1999 Sep;23(1):99-103
references.pmid: 10471508
references.citation: Nature. 2010 May 13;465(7295):182-7
references.pmid: 20393465
references.citation: Nat Neurosci. 2005 Jun;8(6):759-67
references.pmid: 15880109
references.citation: Mol Gen Genet. 1994 May 10;243(3):315-24
references.pmid: 8043104
references.citation: Cell Stem Cell. 2012 Jul 6;11(1):23-35
references.pmid: 22770240
references.citation: Nature. 1995 Jul 27;376(6538):348-51
references.pmid: 7630403
references.citation: Sci Signal. 2012 Jun 19;5(229):ra44
references.pmid: 22715467
references.citation: J Neurochem. 1990 Dec;55(6):1920-7
references.pmid: 2230801
references.citation: Science. 1985 Sep 20;229(4719):1265-8
references.pmid: 4035354
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2306-11
references.pmid: 11226235