A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription

Jianqi Yang; Jie Huang; Tapan K Chatterjee; Erik Twait; Rory A Fisher

doi:10.1074/jbc.M110.121459

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A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription

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A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription

Jianqi Yang, Jie Huang, Tapan K Chatterjee, Erik Twait and Rory A Fisher

The Journal of biological chemistry, Vol.285(39), pp.29760-29769

09/24/2010

DOI: 10.1074/jbc.M110.121459

PMCID: PMC2943308

PMID: 20630860

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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 G i/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.

Gene Regulation

Signal Transduction

Gene Transcription

Transcription Regulation

Bcl6

G Proteins

NF-YA

Transcription Factors

Acetylation

RGS4 Gene

Details

Title: Subtitle: A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription
Creators: Jianqi Yang - University of Iowa
Jie Huang - University of Iowa
Tapan K Chatterjee - University of Cincinnati
Erik Twait - University of Iowa
Rory A Fisher - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.285(39), pp.29760-29769
DOI: 10.1074/jbc.M110.121459
PMID: 20630860
PMCID: PMC2943308
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: GM075033; GM075033-03s1 / National Institutes of Health
Alternative title: Transcriptional Regulation of RGS4
Language: English
Date published: 09/24/2010
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040533502771

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