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Determinants of a transcriptionally competent environment at the GM-CSF promoter

Brettingham-Moore, Kate H; Sprod, O R; Chen, Xinxin; Oakford, P; Shannon, M Frances; Holloway, Adele F

Description

Granulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells, but not B cells, in response to immune signals. GM-CSF gene activation in response to T-cell stimulation requires remodelling of chromatin associated with the gene promoter, and these changes do not occur in B cells. While the CpG methylation status of the murine GM-CSF promoter shows no correlation with the ability of the gene to respond to activation, we find that the basal chromatin environment of...[Show more]

dc.contributor.authorBrettingham-Moore, Kate H
dc.contributor.authorSprod, O R
dc.contributor.authorChen, Xinxin
dc.contributor.authorOakford, P
dc.contributor.authorShannon, M Frances
dc.contributor.authorHolloway, Adele F
dc.date.accessioned2009-06-23T02:08:14Z
dc.date.accessioned2010-12-20T06:03:48Z
dc.date.available2009-06-23T02:08:14Z
dc.date.available2010-12-20T06:03:48Z
dc.identifier.citationNucleic Acids Research 36.8 (2008): 2639-2653
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.urihttp://hdl.handle.net/10440/515
dc.identifier.urihttp://digitalcollections.anu.edu.au/handle/10440/515
dc.description.abstractGranulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells, but not B cells, in response to immune signals. GM-CSF gene activation in response to T-cell stimulation requires remodelling of chromatin associated with the gene promoter, and these changes do not occur in B cells. While the CpG methylation status of the murine GM-CSF promoter shows no correlation with the ability of the gene to respond to activation, we find that the basal chromatin environment of the gene promoter influences its ability to respond to immune signals. In unstimulated T cells but not B cells, the GM-CSF promoter is selectively marked by enrichment of histone acetylation, and association of the chromatin-remodelling protein BRG1. BRG1 is removed from the promoter upon activation concomitant with histone depletion and BRG1 is required for efficient chromatin remodelling and transcription. Increasing histone acetylation at the promoter in T cells is paralleled by increased BRG1 recruitment, resulting in more rapid chromatin remodelling, and an associated increase in GM-CSF mRNA levels. Furthermore, increasing histone acetylation in B cells removes the block in chromatin remodelling and transcriptional activation of the GM-CSF gene. These data are consistent with a model in which histone hyperacetylation and BRG1 enrichment at the GM-CSF promoter, generate a chromatin environment competent to respond to immune signals resulting in gene activation.
dc.format15 pages
dc.publisherOxford University Press
dc.rights"This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited." - from article
dc.sourceNucleic Acids Research
dc.source.urihttp://nar.oxfordjournals.org/cgi/reprint/36/8/2639
dc.source.urihttp://nar.oxfordjournals.org/cgi/content/full/36/8/2639
dc.subjectKeywords: BRG1 protein; granulocyte macrophage colony stimulating factor; histone; messenger RNA; acetylation; animal cell; article; B lymphocyte; chromatin assembly and disassembly; chromatin immunoprecipitation; controlled study; correlation analysis; CpG island;
dc.titleDeterminants of a transcriptionally competent environment at the GM-CSF promoter
dc.typeJournal article
local.identifier.citationvolume36
dcterms.dateAccepted2008-02-29
dc.date.issued2008-03-15
local.identifier.absfor060405
local.identifier.ariespublicationu4020362xPUB104
local.type.statusPublished Version
local.contributor.affiliationBrettingham-Moore, Kate H, University of Tasmania
local.contributor.affiliationSprod, O R, University of Tasmania
local.contributor.affiliationChen, Xinxin, John Curtin School of Medical Research, Division of Molecular Bioscience
local.contributor.affiliationOakford, P, University of Tasmania
local.contributor.affiliationShannon, M Frances, John Curtin School of Medical Research, Division of Molecular Bioscience
local.contributor.affiliationHolloway, Adele F, University of Tasmania
local.bibliographicCitation.issue8
local.bibliographicCitation.startpage2639
local.bibliographicCitation.lastpage2653
local.identifier.doi10.1093/nar/gkn117
dc.date.updated2015-12-08T09:10:29Z
local.identifier.scopusID2-s2.0-43349099904
local.identifier.thomsonID000255759600019
CollectionsANU Research Publications

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