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

Brettingham-Moore, KH, Sprod, OR, Chen, X, Oakford, PC, Shannon, MF and Holloway, AF ORCID: 0000-0003-2213-1717 2008 , 'Determinants of a transcriptionally competent environment at the GM-CSF promote' , Nucleic Acids Research, vol. 36, no. 8 , pp. 2639-2653 , doi:

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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 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

Item Type: Article
Authors/Creators:Brettingham-Moore, KH and Sprod, OR and Chen, X and Oakford, PC and Shannon, MF and Holloway, AF
Journal or Publication Title: Nucleic Acids Research
ISSN: 0305-1048
DOI / ID Number:
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