| Literature DB >> 31377117 |
Franziska Petermann1, Aleksandra Pękowska2, Catrina A Johnson1, Dragana Jankovic3, Han-Yu Shih1, Kan Jiang1, William H Hudson4, Stephen R Brooks5, Hong-Wei Sun5, Alejandro V Villarino1, Chen Yao1, Kentner Singleton1, Rama S Akondy4, Yuka Kanno6, Alan Sher3, Rafael Casellas2, Rafi Ahmed4, John J O'Shea7.
Abstract
Interferon gamma (IFN-γ), critical for host defense and tumor surveillance, requires tight control of its expression. Multiple cis-regulatory elements exist around Ifng along with a non-coding transcript, Ifng-as1 (also termed NeST). Here, we describe two genetic models generated to dissect the molecular functions of this locus and its RNA product. DNA deletion within the Ifng-as1 locus disrupted chromatin organization of the extended Ifng locus, impaired Ifng response, and compromised host defense. Insertion of a polyA signal ablated the Ifng-as1 full-length transcript and impaired host defense, while allowing proper chromatin structure. Transient knockdown of Ifng-as1 also reduced IFN-γ production. In humans, discordant expression of IFNG and IFNG-AS1 was evident in memory T cells, with high expression of this long non-coding RNA (lncRNA) and low expression of the cytokine. These results establish Ifng-as1 as an important regulator of Ifng expression, as a DNA element and transcribed RNA, involved in dynamic and cell state-specific responses to infection. Published by Elsevier Inc.Entities:
Keywords: CTCF; Hi-C; IFN-γ; T helper cells; Th1; Toxoplasma gondii; cytokine; effector memory; genome architecture; lncRNA
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Year: 2019 PMID： 31377117 PMCID： PMC6754279 DOI： 10.1016/j.molcel.2019.06.025
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970