Restraint of IFN-γ expression through a distal silencer CNS-28 for tissue homeostasis.

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 ty

SUBMITTER: Cui K 

PROVIDER: S-EPMC10175192 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature