Fig 3. MYSM1 interacts with H2AK119ub and reduces the level of H2AK119ub at the IL-6 and IL-1β promoters.

(A) MYSM1 expression in PBMCs from control and experimental groups exposed to Staphylococcus aureus SEI antigen for 6 hours, obtained from the GSE11281 dataset; (B) In the LPS-induced secondary infection cell model of sepsis usingPMsderived from WT mice, MYSM1 mRNA expression levels were measured by RT-PCR. (C) In the LPS-induced secondary infection cell model of sepsis usingPMsderived from WT mice, immunoprecipitation (Co-IP) and western blot (WB) analysis were performed to detect the interaction between H2AK119ub and MYSM1. (D, E) In the LPS-induced secondary infection cell model of sepsis usingPMsderived from WT and MYSM1ex2-Δ/Δ mice, H2AK119ub and IL-1β levels were detected by WB, IL-6 protein in the cell supernatant was measured by ELISA. (F, G) Cut&Tag-qPCR analysis of H2AK119ub enrichment at the IL-6 and IL-1β promoter regions inPMsderived from WT and MYSM1ex2-Δ/Δ mice in an LPS-induced secondary infection sepsis model. (H) Mechanistic diagram illustrating that MYSM1 removes H2AK119 ubiquitination at the IL-6and IL-1βpromoter regionsthrough its deubiquitinase activity, thereby suppressing the expression of the inflammatory cytokine IL-6 and IL-1β. Fig 3H: Citation to Use: Created in BioRender. An, Q. (2026) https://BioRender.com/eqf1660. All experiments were repeated at least 3 times with similar results. The data are expressed as means ± SDs. Statistical analysis was performed using two-way ANOVA followed by Tukey’s multiple comparisons test (E, F, G), two-sided Student’s t-test (A), and one-way ANOVA (B). Data were considered statistically significant when *p ≤ 0.05, **p ≤ 0.01,***p ≤ 0.001, and ****p ≤ 0.0001. https://doi.org/10.6084/m9.figshare.30581489.