转录辅因子对不同类型的核心促进体具有特异性
Vanja Haberle1, Cosmas D Arnold1, Michaela Pagani1
1Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Nature
|May 17, 2019
概括
转录辅助因子 (COF) 对不同类型的促进体表现出特定的偏好. 这种COF促进器的兼容性影响了包括人类在内的各个物种的基因表达程序.
科学领域:
- 分子生物学
- 遗传学
- 表观遗传学
背景情况:
- 转录辅助因子 (COF) 通过将信号从增强剂传递给促进剂,对基因表达至关重要.
- 之前的研究表明,一些COF可能有利于特定的促进体类型,但缺乏对COF促进体特异性的全面了解.
研究的目的:
- 调查不同COF和各种核心促进体 (CP) 类型之间的内在特异性的程度.
- 确定COF促销器兼容性是否影响基因调节和转录程序.
主要方法:
- 在Drosophila melanogaster S2细胞中使用高吞吐量促进体活性测试,对72,000个候选核心促进体进行查.
- 分析包括识别与不同CP类型相关的序列元素和染色质特性 (H3K4me3,H3K4me1).
- 在额外的Drosophila和人类细胞系中验证了COF促进剂的兼容性.
主要成果:
- 通过COF对CP的差异激活显示出明显的COF促进剂兼容性.
- 对特定的序列元素 (TATA盒,DPE,TCT) 进行了功能上不同的CP类型的丰富,并表现出独特的染色体标记.
- 在和人类细胞中,COF显示出对特定促进体类型 (例如TATA盒或CpG岛促进体) 的偏好.
结论:
- 增强剂与COF促进剂的兼容性是解释增强剂如何特别激活不同基因组的一个基本机制.
- 这些兼容性有助于基因内的替代性促进体使用和不同的转录起点.
- 从到人类的转录程序的基础上,COF促进剂相互作用代表了保存的调节原则.
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