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The magnitude of IFN-g responses is fine-tuned by DNA architecture and the non-coding transcript of Ifng-as1

ABSTRACT: IFN-g, 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 IFN-g 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-g production. In humans, discordant expression of IFNG and IFNG-AS1 was evident in memory T cells, with high expression of this 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE132531 | GEO | 2019/07/19

REPOSITORIES: GEO

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The magnitude of IFN-g responses is fine-tuned by DNA architecture and the non-coding transcript of Ifng-as1

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