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超强增强剂中的转录凝聚物在先天免疫中介于pH依赖的转录控制
Shengyuan Wang1, Zhongyang Wu2,3, Zhe Zhong2,3
1Department of Genome Sciences, University of Virginia, Charlottesville, VA 22908, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
组织酸化通过破坏BRD4转录凝聚物来削弱巨细胞的免疫反应. 像RELA和IRF3这样的关键调节者在酸性条件下表现出减少的结合,影响免疫基因表达.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 组织酸化在缺氧,炎症和瘤中很常见.
- 酸性pH通过削弱BRD4依赖的转录凝缩物,影响巨细胞的先天免疫力.
- 连接凝结物干扰与特定免疫基因调节的机制尚不清楚.
研究的目的:
- 确定具有pH敏感调节潜力的转录调节器 (TRs).
- 调查TR与BRD4依赖的转录凝聚物的关联.
- 阐明酸性压力如何调节巨细胞的免疫反应.
主要方法:
- 综合ATAC-seq,ChIP-seq和RNA-seq分析在初级小鼠巨细胞中.
- 表观基因组分析以确定基于BRD4和h3K27ac.ac.的pH依赖性超级增强剂 (SE).
- 在不同的pH条件下评估候选TRs (RELA,IRF,STAT家族) 的结合.
主要成果:
- 确定了RELA,IRF和STAT家族作为BRD4相关的pH敏感SE的候选TRs.
- 在酸性条件下,RELA和IRF3的结合显著下降 (pH为6.5而不是7.4),反映了BRD4的变化.
- 在这些SE中,免疫基因 (例如,Ch25h,Ifit家族) 在中性pH下表达更高.
结论:
- 在BRD4相关的pH敏感凝聚物中,一组TRs协调巨细胞基因激活.
- 酸性压力会破坏这些凝聚物,导致免疫基因表达的改变.
- 提供了关于pH如何通过转录调节影响巨细胞免疫反应的机制性见解.
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