| First Author | Cui K | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 5 | Pages | 944-958.e6 |
| PubMed ID | 37040761 | Mgi Jnum | J:335541 |
| Mgi Id | MGI:7470619 | Doi | 10.1016/j.immuni.2023.03.006 |
| Citation | Cui K, et al. (2023) Restraint of IFN-gamma expression through a distal silencer CNS-28 for tissue homeostasis. Immunity 56(5):944-958.e6 |
| abstractText | Interferon-gamma (IFN-gamma) is a key cytokine in response to viral or intracellular bacterial infection in mammals. While a number of enhancers are described to promote IFN-gamma responses, to the best of our knowledge, no silencers for the Ifng gene have been identified. By examining H3K4me1 histone modification in naive CD4(+) T cells within Ifng locus, we identified a silencer (CNS-28) that restrains Ifng expression. Mechanistically, CNS-28 maintains Ifng silence by diminishing enhancer-promoter interactions within Ifng locus in a GATA3-dependent but T-bet-independent manner. Functionally, CNS-28 restrains Ifng transcription in NK cells, CD4(+) cells, and CD8(+) T cells during both innate and adaptive immune responses. Moreover, CNS-28 deficiency resulted in repressed type 2 responses due to elevated IFN-gamma expression, shifting Th1 and Th2 paradigm. Thus, CNS-28 activity ensures immune cell quiescence by cooperating with other regulatory cis elements within the Ifng gene locus to minimize autoimmunity. |
