一种近位增强剂在早期人类Th17细胞分化过程中调节RORA表达
Ubaid Ullah Kalim1, Rahul Biradar1, Sini Junttila1
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
Clinical immunology (Orlando, Fla.)
|May 24, 2024
概括
研究人员确定了控制T助手17 (Th17) 细胞分化的关键增强剂. 他们在这些Th17增强剂中发现了与自身免疫性疾病相关的遗传变异,包括一个调节RORA的变异,为Th17细胞命运提供了洞察力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 基因调控元素,如增强剂,通过调节基因表达来对细胞身份至关重要.
- 人类T助手17 (Th17) 细胞分化过程中增强剂活性的动态变化尚未完全理解.
研究的目的:
- 识别和描述参与Th17细胞分化中的增强剂.
- 研究这些增强剂在自身免疫性疾病中的遗传变异的作用.
- 阐明RORA在Th17细胞发育中的调节机制.
主要方法:
- 使用ATAC-seq.进行染色体可访问性分析.
- 分析关键的质子修饰.
- 用CRISPR-Cas9编辑识别和功能验证Th17特异性增强剂,包括一个用于RORA的增强剂.
主要成果:
- 确定了一组控制Th17细胞命运规范的增强剂.
- 在Th17增强剂中发现了与自身免疫性疾病相关的23个单核酸多态 (SNP),与转录因子结合部位重叠.
- 在RORA内的一种特定增强剂被证明可以积极调节RORA转录,由CRISPR-Cas9删除证实.
结论:
- 这项研究揭示了控制Th17细胞分化的关键增强剂.
- Th17增强剂中的遗传变异可能导致自身免疫性疾病.
- 已识别的RORA增强剂在调节RORA转录和协调Th17细胞分化方面发挥着关键作用.
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