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

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)16181-16186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number40
DOIs
StatePublished - Oct 1 2013

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Immediate-Early Genes
Histone Acetyltransferases
Brain
inositol polyphosphate multikinase
Epigenomics
Transcriptional Activation

Keywords

  • Inositol phosphates
  • Learning

ASJC Scopus subject areas

  • General

Cite this

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction. / Xu, Risheng; Paul, Bindu; Smith, Dani R.; Tyagi, Richa; Rao, Feng; Khan, A. Basit; Blech, Daniel J.; Vandiver, M. Scott; Harraz, Maged; Guha, Prasun; Ahmed, Ishrat; Sen, Nilkantha; Gallagher, Michela; Snyder, Solomon H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 40, 01.10.2013, p. 16181-16186.

Research output: Contribution to journalArticle

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