Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Risheng Xu; Bindu D. Paul; Dani R. Smith; Richa Tyagi; Feng Rao; A. Basit Khan; Daniel J. Blech; M. Scott Vandiver; Maged M. Harraz; Prasun Guha; Ishrat Ahmed; Nilkantha Sen; Michela Gallagher; Solomon H. Snyder

doi:10.1073/pnas.1315551110

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Risheng Xu, Bindu D. Paul, Dani R. Smith, Richa Tyagi, Feng Rao, A. Basit Khan, Daniel J. Blech, M. Scott Vandiver, Maged M. Harraz, Prasun Guha, Ishrat Ahmed, Nilkantha Sen, Michela Gallagher, Solomon H. Snyder

Graduate Studies

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31 Scopus citations

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.

Original language	English (US)
Pages (from-to)	16181-16186
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	40
DOIs	https://doi.org/10.1073/pnas.1315551110
State	Published - Oct 1 2013

Keywords

Inositol phosphates
Learning

ASJC Scopus subject areas

General

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10.1073/pnas.1315551110

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Xu, R., Paul, B. D., Smith, D. R., Tyagi, R., Rao, F., Khan, A. B., Blech, D. J., Vandiver, M. S., Harraz, M. M., Guha, P., Ahmed, I., Sen, N., Gallagher, M., & Snyder, S. H. (2013). Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction. Proceedings of the National Academy of Sciences of the United States of America, 110(40), 16181-16186. https://doi.org/10.1073/pnas.1315551110

Xu, R, Paul, BD, Smith, DR, Tyagi, R, Rao, F, Khan, AB, Blech, DJ, Vandiver, MS, Harraz, MM, Guha, P, Ahmed, I, Sen, N, Gallagher, M & Snyder, SH 2013, 'Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 40, pp. 16181-16186. https://doi.org/10.1073/pnas.1315551110

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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.",

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AU - Vandiver, M. Scott

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AU - Snyder, Solomon H.

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AB - 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.

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Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

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