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Wando Mount Pleasant Library
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Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis.
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- Author(s): Cui, Kairong1 (AUTHOR); Chen, Zuojia1,2 (AUTHOR); Cao, Yaqiang1 (AUTHOR); Liu, Shuai1 (AUTHOR); Ren, Gang1 (AUTHOR); Hu, Gangqing1 (AUTHOR); Fang, Difeng3 (AUTHOR); Wei, Danping3 (AUTHOR); Liu, Chengyu4 (AUTHOR); Zhu, Jinfang3 (AUTHOR); Wu, Chuan1,2 (AUTHOR) ; Zhao, Keji1 (AUTHOR)
- Source:
Immunity (10747613). May2023, Vol. 56 Issue 5, p944-944. 1p.- Subject Terms:
- Source:
- Additional Information
- Abstract: Interferon-γ (IFN-γ) is a key cytokine in response to viral or intracellular bacterial infection in mammals. While a number of enhancers are described to promote IFN-γ 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-γ 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. [Display omitted] • Identification of the Ifng silencer CNS–28 • CNS–28 represses interaction between CNS–22 and Ifng promoter • CNS–28 maintains tissue quiescence by restraining IFN-γ production • CNS–28 deletion represses type 2 responses via enhanced IFN-γ expression There are multiple enhancer regions for the Ifng locus, but Ifng restraint is unknown. Cui et al. identify a silencer CNS–28 that diminishes enhancer-promoter interactions within Ifng locus in a GATA3-dependent but T-bet-independent manner. Together with other regulatory elements, CNS–28 activity ensures immune cell quiescence and minimizes autoimmunity. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Immunity (10747613) is the property of Cell Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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