Foxp3利用了对于监管性T细胞系谱规范的先前存在的增强器格局
Robert M Samstein1, Aaron Arvey, Steven Z Josefowicz
1Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|October 2, 2012
概括
调节性T (Treg) 细胞依赖Foxp3进行免疫平衡. Foxp3主要利用现有的增强剂,而不是创建新的增强剂,在分化过程中定义Treg细胞功能.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 调节性T (Treg) 细胞对于维持免疫平衡至关重要.
- 转录因子Foxp3定义了Treg细胞的身份和功能.
- 通过Foxp3建立Treg特异性基因表达的机制尚不清楚.
研究的目的:
- 调查Foxp3是否积极修改染色体格局或利用Treg谱系规范的先前存在的增强剂.
- 了解Foxp3与增强剂的结合如何促进Treg细胞分化.
主要方法:
- 在Treg和Foxp3-阴性T细胞中进行染色质可访问性分析.
- 识别Foxp3结合增强剂及其由辅助因子占用.
- 分析T细胞激活和分化过程中增强器可访问性动态的分析.
主要成果:
- Foxp3主要与已经可访问的增强剂结合,并在前体细胞中被辅助因子占据.
- 大多数与Foxp3结合的Treg细胞增强剂在Foxp3表达之前在T细胞受体激活时变得可用.
- 一小部分增强剂仅针对Treg细胞,与关键功能基因相关.
结论:
- 福克斯p3的功能是"机会主义的",主要是利用Treg细胞规范的先前存在的增强器网络.
- Foxp3并没有建立新的增强器景观,而是在后期分化过程中利用现有的景观.
- 这种机制突显了转录因子如何通过利用动态染色质可访问性来定义细胞身份.
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