| First Author | Petermann F | Year | 2019 |
| Journal | Mol Cell | Volume | 75 |
| Issue | 6 | Pages | 1229-1242.e5 |
| PubMed ID | 31377117 | Mgi Jnum | J:283672 |
| Mgi Id | MGI:6376733 | Doi | 10.1016/j.molcel.2019.06.025 |
| Citation | Petermann F, et al. (2019) The Magnitude of IFN-gamma Responses Is Fine-Tuned by DNA Architecture and the Non-coding Transcript of Ifng-as1. Mol Cell 75(6):1229-1242.e5 |
| abstractText | Interferon gamma (IFN-gamma), 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-gamma 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. |
