The aetiology of inflammatory bowel disease (IBD) is related to genetics and epigenetics. Epigenetic regulation of the pathogenesis of IBD has not been well defined. Here, we investigated the role of H3K27ac events in the pathogenesis of IBD. Based on previous ChIP-seq and RNA-seq assays, we studied signal transducer and activator of transcription 1 (STAT1) as a transcription factor (TF) and investigated whether the STAT1–EP300–H3K27ac axis contributes to the development of IBD. We performed ChIP-PCR to investigate the interaction between STAT1 and H3K27ac, and co-IP assays were performed to investigate the crosstalk between STAT1 and EP300. Lymphocyte cytosolic protein 2 (LCP2) and TNF-α‐inducible protein 2 (TNFAIP2) are target genes of STAT1. p-STAT1 binds to the enhancer loci of the two genes where H3K27ac is enriched, and EP300 subsequently binds to regulate their expression. In mice with dextran sulfate sodium (DSS)-induced acute colitis, an EP300 inhibitor significantly inhibited colitis. p-STAT1 and EP300 promote TNFAIP2 and LCP2 expression through an increase in H3K27ac enrichment on their enhancers and contribute to the pathogenesis of chronic inflammation.

中文翻译：

---

STAT1 通过招募 EP300 在表观遗传上调节 LCP2 和 TNFAIP2 参与炎症性肠病的发病机制

炎症性肠病 (IBD) 的病因与遗传学和表观遗传学有关。IBD发病机制的表观遗传调控尚未明确。在这里，我们研究了 H3K27ac 事件在 IBD 发病机制中的作用。基于之前的 ChIP-seq 和 RNA-seq 分析，我们研究了信号转导和转录激活因子 1 (STAT1) 作为转录因子 (TF)，并研究了 STAT1-EP300-H3K27ac 轴是否有助于 IBD 的发展。我们进行了 ChIP-PCR 以研究 STAT1 和 H3K27ac 之间的相互作用，并进行了 co-IP 测定以研究 STAT1 和 EP300 之间的串扰。淋巴细胞胞质蛋白 2 (LCP2) 和 TNF-α 诱导蛋白 2 (TNFAIP2) 是 STAT1 的靶基因。p-STAT1 与富集 H3K27ac 的两个基因的增强子基因座结合，和 EP300 随后结合以调节它们的表达。在葡聚糖硫酸钠 (DSS) 诱导的急性结肠炎小鼠中，EP300 抑制剂显着抑制结肠炎。p-STAT1 和 EP300 通过增加其增强子上的 H3K27ac 富集来促进 TNFAIP2 和 LCP2 的表达，并有助于慢性炎症的发病机制。