凝聚素介导的染色质重塑控制了传统树突细胞的分化和功能
Nicholas M Adams1, Aleksandra Galitsyna2, Ioanna Tiniakou1
1Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
bioRxiv : the preprint server for biology
|September 30, 2024
概括
凝聚蛋白复合体对树突细胞分化和功能至关重要,影响抗原呈现和IL-12分泌. 这种染色体组织剂与转录因子相互作用,使细胞发育和免疫反应正常.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 凝聚体复合物通过挤出染色素环来将染色体组织成拓相关的域.
- 凝聚素介导的染色质组织,特别是免疫细胞中的精确生物学作用仍然不清楚.
研究的目的:
- 研究凝聚素在抗原呈现树突细胞 (DC) 的分化和功能中的作用.
- 阐明凝聚素,CTCF和转录因子在塑造DC染色质和功能的相互作用.
主要方法:
- 在活体中研究了凝聚素在异位后分化和树突细胞 (DC) 功能中的作用.
- 分析了凝聚素和IRF8对DC染色质循环和分隔的影响.
- 研究了DC激活期间的基因表达变化以及对凝聚素和远端增强剂的要求.
主要成果:
- 凝聚素对于树突细胞 (DC) 的分化和功能至关重要,包括抗原交叉呈现和IL-12的分泌通过1型常规DCs (cDC1s) in vivo.
- 凝聚素和转录因子IRF8形成DC染色体组织,控制循环和分隔.
- 最佳的IRF8表达取决于CTCF/凝聚蛋白位点,而凝聚蛋白在DC激活过程中通过远端增强剂调节基因诱导.
结论:
- 凝聚素在体内细胞分化和免疫功能中发挥着至关重要的作用,特别是在树突细胞中.
- 凝聚素介导的染色质调节表现出双向交叉声调与特定谱系的转录因子,如IRF8.
- 破坏CTCF/凝聚蛋白位点,例如在Il12b基因附近,会损害cDC1s中IL-12的产生.
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