Linked Life Data

20630860

Source:http://linkedlifedata.com/resource/pubmed/id/20630860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2010-9-20
pubmed:abstractText
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/EBP? and decreases in Bcl6 levels in the nucleus. Increases in NF-YA and C/EBP? 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/BCL6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Binding Factor, http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta, http://linkedlifedata.com/resource/pubmed/chemical/CEBPB protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cebpb protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/NFYA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RGS Proteins, http://linkedlifedata.com/resource/pubmed/chemical/RGS4 protein, http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29760-9
pubmed:dateRevised
2011-9-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription.
pubmed:affiliation
Departments of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural