Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction.
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.
['Xu|Risheng|R|', 'Paul|Bindu D|BD|', 'Smith|Dani R|DR|', 'Tyagi|Richa|R|', 'Rao|Feng|F|', 'Khan|A Basit|AB|', 'Blech|Daniel J|DJ|', 'Vandiver|M Scott|MS|', 'Harraz|Maged M|MM|', 'Guha|Prasun|P|', 'Ahmed|Ishrat|I|', 'Sen|Nilkantha|N|', 'Gallagher|Michela|M|', 'Snyder|Solomon H|SH|']
D000704:Analysis of Variance D000818:Animals D001921:Brain D050882:CREB-Binding Protein D047369:Chromatin Immunoprecipitation D044127:Epigenesis, Genetic D005786:Gene Expression Regulation D017781:Genes, Immediate-Early D018782:Maze Learning D051379:Mice D017853:Phosphotransferases (Alcohol Group Acceptor) D021641:Recognition, Psychology D015533:Transcriptional Activation
inositol phosphates learning