Fig. 7

BRD4 inhibition disrupted IRF4 SE formation in M2 AMs. a Super enhancers of M0, M2, and ARV825-M2 macrophage, which are ranked by their H3K27ac signaling using ROSE. b Venn diagram showed the overlap of genes associated with SEs sites, M2-specific genes, and ARV825 downregulated genes in M2. c Gene tracks of Irf4 associated SE in M2 AMs. The adjacent genes IRF4 showed strong SE peaks and RNA-seq signals in M2 AMs and intensively reduced when using ARV-825. d Volcano plot depicting significant downregulation of Irf4 in M2 macrophage by BRD4 inhibition drug ARV825. e Venn diagram showed overlapped peaks of BRD4, H3K27ac, and IRF4 in M2 AMs. f Binding intensity of IRF4 across the BRD4 binding sites of the whole genome in AMs from the M0 group, M2 group, and ARV-825 + M2 group. g Gene tracks of Mmp12 in the M2 AMs. The adjacent gene Mmp12 showed strong IRF4 peaks and RNA-seq signals in the M2 AMs. h Barplot showed expression of Irf4, Mmp12, and Tfrc in response to IRF4 transfection in M2 AMs with or without treatment with ARV825 (n = 5). i Transcription level of Irf4, Mmp12 was significantly downregulated by BRD4 inhibition drugs in pulmonary sections from LPS/elastase-induced COPD mice. The values were detected by quantitative PCR (n = 5). j Box plots showed the abundance of IRF4 (Guangzhou p = 0.006; Shenzhen p = 0.0012), and MMP12 (Guangzhou p = 0.00056; Shenzhen p = 0.00022) in COPD and healthy control. k The gene expression of IRF4 and MMP12 were significantly correlated in Guangzhou and Shenzhen COPD patients. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001