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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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Copyright Statement
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 |
| UTAS Author: | Poke, FS (Dr Fiona Poke) |
| UTAS Author: | Upcher, WR (Mr William Upcher) |
| UTAS Author: | Sprod, OR (Mr Owen Sprod) |
| UTAS Author: | Young, A (Miss Arabella Young) |
| UTAS Author: | Brettingham-Moore, KH (Dr Kate Brettingham-Moore) |
| UTAS Author: | Holloway, AF (Professor Adele Holloway) |
| ID Code: | 79014 |
| Year Published: | 2012 |
| Funding Support: | National Health and Medical Research Council (490014) |
| Web of Science® Times Cited: | 5 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2012-08-13 |
| Last Modified: | 2017-11-07 |
| Downloads: | 352 View Download Statistics |
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