Fig 2: Model explaining how p-STAT1 interacts with EP300 to promote H3K27ac enrichment on the enhancers of LCP2 and TNFAIP2 and contributes to the development of chronic inflammation. When STAT1 is activated by IFN-?, STAT1 migrates into the nucleus and binds to the enhancers of LCP2 and TNFAIP2. p-STAT1 interacts with EP300 to promote H3K27ac enrichment on the enhancers and promote the transcriptions of LCP2 and TNFAIP2 and then contributes to the development of chronic inflammation

Fig 3: Identification of LCP2 and TNFAIP2 as STAT1 target genes. a Overlap of the target of STAT1 on the website of GTRD and the upregulated genes in the RNA-seq whose enhancers had increased H3K27ac enrichment after DSS treatment. b TNFAIP2, LCP2, CREBBP, HNF4A, LRG1, HSD17, USP18 mRNA expression in NCM460 cell inflammation model (error bars: mean ± SD). c-d LCP2 and TNFAIP2 mRNA and protein expression in DSS-induced mice chronic colitis (error bars: mean ± SEM; control group n = 7, DSS group n = 9). e–f LCP2 and TNFAIP2 mRNA and protein expression in IBD patients (error bars: mean ± SEM; NC group n = 8, UC group n = 8, CD group n = 10). g The correlation between STAT1 and LCP2, TNFAIP2 in UC and CD patients in GEO database. h–i STAT1 mRNA and protein expression in NCM460 after transfected with siSTAT1-1, 2, 3 or the negative control (error bars: mean ± SD). j–k LCP2 and TNFAIP2 mRNA and protein expression in NCM460 after transfected with siSTAT1-1, 2 or the negative control with stimulation by IFN-γ (error bars: mean ± SD). l–m LCP2 and TNFAIP2 mRNA and protein expression in NCM460 after transfected with siSTAT1-1, 2 or the negative control with stimulation by TNF-α and IFN-γ (error bars: mean ± SD). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Fig 4: PBA enhances the acetylation of CBP/p300 and histone H3 at the CPT1A and INSIG2 promoters in Huh7-shTSC2 cells. PBA (8 mM, 6 h) induced the gene expression of CPT1A and INSIG2 (A), and the acetylation status of histone H3 and histone H4 (B). Chromatin immunoprecipitation (ChIP) assay revealed PBA-mediated enrichment of acetyl CBP/p300 (Ac-p300) and acetyl histone H3 (Ac-H3) at the CPT1A and INSIG2 promoters (C). Statistical significance was determined using Student’s t-test, * p < 0.05, n = 4.

Fig 5: Carnosol is a specific p300 inhibitor in vitro. (A) Carnosol inhibit histone acetylation in vitro. HAT assay with HeLa nuclear extract in the presence of increasing concentrations of carnosol. Values represented in percent were calculated from three independent experiments carried out in triplicate and are represented as mean ± SEM. (**p < 0.005, ***p < 0.001). (B–D) Carnosol inhibits P300 (B) but not PCAF (C) or GCN5 (D). HAT assay was performed with p300 catalytic domain (aa 1,284–1,673), recombinant PCAF and recombinant GCN5, recombinant H3 with or without increasing carnosol. HAT activity was measured by Western Blotting scoring for acetylated histone H3. (E) HAT assay was performed with recombinant p300 catalytic domain (aa 1,284–1,673) and core histone with or without carnosol and HAT activity was measured as in (B). Data shown for all HAT assays are representative of three independent experiments. The intensities of the bands were quantified using the ImageJ software (National Institute of Health, USA).