A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription

Jianqi Yang, Jie Huang, Tapan Kumar Chatterjee, Erik Twait, Rory A. Fisher

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Neuronally enriched RGS4 plays a critical role attenuating G protein signaling in brain, although the mechanisms regulating RGS4 expression are unknown. Here we describe a novel mechanism for transcriptional activation of RGS4 in neuron-like PC6 cells, where RGS4 is markedly induced during confluence-induced growth arrest. Transcriptional activation of RGS4 in confluent PC6 cells was accompanied by impaired Gi/o-dependent MAPK activation. In the human RGS4 gene promoter, we identified three phylogenetically conserved cis-elements: an inverted CCAAT box element (ICE), a cAMP response element, and a B-cell lymphoma 6 (Bcl6)-binding site. The ICE and the cAMP response element mediate activation, and the Bcl6 site mediates repression of RGS4 transcription. Activation of RGS4 transcription in confluent PC6 cells is accompanied by increases in NF-YA and C/EBPβ and decreases in Bcl6 levels in the nucleus. Increases in NF-YA and C/EBPβ lead to their increased binding to the RGS4 promoter in vivo, and dominant negative forms of these proteins repressed RGS4 promoter activity. Acetylation of NF-YA and Bcl6 were increased in postconfluent cells. Trichostatin A stimulation of RGS4 promoter activity, accompanied by increased binding of NF-YA and decreased binding of Bcl6 to the promoter, was abolished by mutation of the ICE and enhanced by mutation of the Bcl6 site. These findings demonstrate a dynamic and coordinated regulation of nuclear levels and acetylation status of trans-acting factors critical in determining the off/on state of the RGS4 promoter.

Original languageEnglish (US)
Pages (from-to)29760-29769
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number39
DOIs
StatePublished - Sep 24 2010

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Acetylation
B-Cell Lymphoma
Transcription
Chemical activation
Transcriptional Activation
Response Elements
trichostatin A
Trans-Activators
Mutation
GTP-Binding Proteins
Neurons
Brain
Genes
Binding Sites
Cells
PC6 extract
Growth
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription. / Yang, Jianqi; Huang, Jie; Chatterjee, Tapan Kumar; Twait, Erik; Fisher, Rory A.

In: Journal of Biological Chemistry, Vol. 285, No. 39, 24.09.2010, p. 29760-29769.

Research output: Contribution to journalArticle

Yang, Jianqi ; Huang, Jie ; Chatterjee, Tapan Kumar ; Twait, Erik ; Fisher, Rory A. / A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 39. pp. 29760-29769.
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