dc.contributor.author | Gibbons, Hunter R. | |
dc.contributor.author | Mi, Deborah J. | |
dc.contributor.author | Farley, Virginia M. | |
dc.contributor.author | Esmond, Tashawna | |
dc.contributor.author | Kaood, Mary B. | |
dc.contributor.author | Aune, Thomas M. | |
dc.date.accessioned | 2020-06-04T15:32:42Z | |
dc.date.available | 2020-06-04T15:32:42Z | |
dc.date.issued | 2019-07-16 | |
dc.identifier.citation | Gibbons HR, Mi DJ, Farley VM, Esmond T, Kaood MB, Aune TM. Bromodomain inhibitor JQ1 reversibly blocks IFN-γ production. Sci Rep. 2019;9(1):10280. Published 2019 Jul 16. doi:10.1038/s41598-019-46516-x | en_US |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/1803/10034 | |
dc.description.abstract | As a class, 'BET' inhibitors disrupt binding of bromodomain and extra-terminal motif (BET) proteins, BRD2, BRD3, BRD4 and BRDT, to acetylated histones preventing recruitment of RNA polymerase 2 to enhancers and promoters, especially super-enhancers, to inhibit gene transcription. As such, BET inhibitors may be useful therapeutics for treatment of cancer and inflammatory disease. For example, the small molecule BET inhibitor, JQ1, selectively represses MYC, an important oncogene regulated by a super-enhancer. IFN-gamma, a critical cytokine for both innate and adaptive immune responses, is also regulated by a super-enhancer. Here, we show that JQ1 represses IFN-gamma expression in TH1 polarized PBMC cultures, CD4+ memory T cells, and NK cells. JQ1 treatment does not reduce activating chromatin marks at the IFNG locus, but displaces RNA polymerase II from the locus. Further, IFN-gamma expression recovers in polarized TH1 cultures following removal of JQ1. Our results show that JQ1 abrogates IFN-gamma expression, but repression is reversible. Thus, BET inhibitors may disrupt the normal functions of the innate and adaptive immune response. | en_US |
dc.description.sponsorship | We thank the subjects who provided blood samples to enable this study. This study was supported by grants from the National institutes of Health, R01AI044942, R21AI128281, and 5P60DK020593. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Scientific Reports | en_US |
dc.rights | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.source.uri | https://pubmed.ncbi.nlm.nih.gov/31311960/ | |
dc.subject | NATURAL-KILLER-CELLS | en_US |
dc.subject | SELECTIVE-INHIBITION | en_US |
dc.subject | SUPER-ENHANCERS | en_US |
dc.subject | TRANSCRIPTIONAL ELONGATION | en_US |
dc.subject | INTERFERON-GAMMA | en_US |
dc.subject | CUTTING EDGE | en_US |
dc.subject | P-TEFB | en_US |
dc.subject | BRD4 | en_US |
dc.subject | IDENTITY | en_US |
dc.subject | MEDIATOR | en_US |
dc.title | lBromodomain inhibitor JQ1 reversibly blocks IFN-gamma production | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41598-019-46516-x | |