Fig 2: 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-? (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-a and IFN-? (error bars: mean ± SD). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Fig 3: Sequence and phylogeny tree of bbslp76. (a) Nucleotide and amino acid sequence of bbslp76. Itk binding motif DYEPPP was marked in the red frame. (b) Protein structures of bbslp76 and hslp76 generated by SMART. (c) Sequences alignment of bbslp76 and hslp76. The color of Sky blue represents 50% consensus of amino acid and dark blue represents 100% consensus of amino acid. Itk binding motif DYEPPP motif was highlight with ******. (d) Phylogenetic tree of slp76. The neighbor-joining phylogenetic tree was constructed on the basis of 13 different slp76 sequences from GenBank, utilizing the sequence analysis tool MEGA 5.

Fig 4: Inhibition of EP300 relieves DSS-induced colitis in mice. a Methods for DSS-induced acute colitis in C57BL/6 mice and C646 administration. b Body weight and c disease activity index of mice that received regular drinking water alone (water group n = 10) or 3.0% DSS-containing water (DSS group n = 10), or 3.0% DSS combined with C646 injection (DSS + C646 group n = 15). For statistical comparisons, asterisk indicates DSS vs. DSS + C646. d Colon length and e representative hematoxylin and eosin (H&E) staining of distal colon sections at day 11 after DSS induction (water group and DSS group n = 10, DSS + C646 group n = 15). f Colonic inflammatory cytokine analysis from colonic tissue at day 11 after DSS induction (n = 10 per group). g LCP2 and TNFAIP2 mRNA expression in colonic tissue at day 11 after DSS induction (n = 10 per group). Error bars: mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns means no significance

Fig 5: STAT1 regulates its target genes through H3K27ac at their enhancers in mice with DSS-induced chronic colitis. a UCSC browser view showing the ChIP-seq density of H3K27ac signal in both control tissue and DSS-induced tissue located in LCP2 and TNFAIP2 gene locus. b ChIP-PCR was performed to validate H3K27ac modification at the LCP2 and TNFAIP2 enhancer in DSS-induced mice chronic colitis. c ChIP-PCR was performed to validate the occupancy of p-STAT1 on the LCP2 and TNFAIP2 enhancer where H3K27ac enriched in DSS-induced mice chronic colitis. Error bars: mean ± SEM; n = 6 per group. *p < 0.05, **p < 0.01