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Depletion of c-Rel from cytokine gene promoters is required for chromatin reassembly and termination of gene responses to T cell activation

Citation

Poke, FS and Upcher, WR and Sprod, OR and Young, A and Brettingham-Moore, KH and Holloway, AF, Depletion of c-Rel from cytokine gene promoters is required for chromatin reassembly and termination of gene responses to T cell activation, PLoS One, 7, (7) Article e41734. ISSN 1932-6203 (2012) [Refereed Article]


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Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0041734

Abstract

The role of the Nuclear Factor κB (NF-κB) transcription factor family in T cell function has been well described. The c-Rel family member is of particular importance in initiating T cell responses to antigen and regulating activation of inflammatory cytokine genes, including the Interleukin-2 (IL-2) and Granulocyte macrophage colony stimulating factor (GM-CSF) genes. c-Rel is required for chromatin remodeling of these gene promoters, which involves depletion of histones from the promoters in response to T cell activating signals. These chromatin remodeling events precede transcriptional activation of the genes. The subsequent down-regulation of cytokine gene expression is important in the termination of an immune response and here we examine this process at the murine GM-CSF and IL-2 genes. We show that the cytokine mRNA levels rapidly return to basal levels following stimulus removal and this is associated with reassembly of histones onto the promoter. Histone reassembly at the GM-CSF and IL-2 promoters occurs concomitantly with depletion of RelA, c-Rel and RNA polymerase II from the promoters. Furthermore we show that transcriptional down-regulation and chromatin reassembly is dependent on depletion of c-Rel from the nucleus, and that this is regulated by the nuclear translocation of the NF-κB inhibitor, IκBα. The nuclear activation of c-Rel therefore not only regulates the initiation of GM-CSF and IL-2 gene activation in response to T cell activation, but also the termination of these gene responses following the removal of the activating signal.

Item Details

Item Type:Refereed Article
Keywords:cytokine, chromatin , gene regulation, GM-CSF
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genome Structure and Regulation
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Poke, FS (Dr Fiona Poke)
Author:Upcher, WR (Mr William Upcher)
Author:Sprod, OR (Mr Owen Sprod)
Author:Young, A (Miss Arabella Young)
Author:Brettingham-Moore, KH (Dr Kate Brettingham-Moore)
Author:Holloway, AF (Associate Professor Adele Holloway)
ID Code:79014
Year Published:2012
Funding Support:National Health and Medical Research Council (490014)
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-08-13
Last Modified:2017-11-07
Downloads:228 View Download Statistics

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