组织素H2BArg95残留物有效地招募转录因子Spt16,以调解Pheromone响应路径的Ste5表达
Abdallah Alhaj Sulaiman1, Reem Ali1, Dindial Ramotar2
1Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, P.O. Box: 34110, Doha, Qatar.
Scientific reports
|June 22, 2023
概括
酵母中的Histone H2B R95A突变会影响基因表达,从而产生对拉巴胺的耐药性. 这通过削弱H2B-Spt16相互作用而发生,影响STE5表达和细胞循环停止.
科学领域:
- 分子生物学分子生物学
- 酵母遗传学 酵母遗传学
- 细胞循环规则 细胞循环规则
背景情况:
- 拉帕米辛抑制了酵母中的TORC1基因酶,导致G1停止和基因表达变化.
- 一个先前已识别的 histone H2B R95A 突变体显示对拉帕米的耐药性.
- 这种抗性与费洛蒙反应途径基因的缺陷有关,包括STE5.
研究的目的:
- 调查基因组 H2B R95A 突变体中拉巴辛耐药性的分子机制.
- 探索FACT复合体成分Spt16在调节STE5表达和拉巴胺素敏感性方面的作用.
- 为了阐明基因素H2B,Spt16和STE5之间的相互作用,在拉帕素诱导的细胞循环停止的背景下.
主要方法:
- 针对拉帕素耐药性的基因组H2B突变体的表征.
- 对野生类型和突变酵母菌株的基因表达,特别是STE5的分析.
- 使用突变收集的基因组H2B和Spt16之间的相互作用的研究.
- 评估spt16突变对拉巴胺素敏感性和Ste5表达的影响.
主要成果:
- H2B R95A突变削弱了组织素H2B和Spt16之间的关联,这是FACT复合物的子单元.
- 在Spt16中发生的突变 (spt16 E857K,spt16-11) 赋予了对拉巴素的敏感性.
- 在spt16突变中观察到改变了Ste5表达,并且抑制器突变 (H2B A84D) 废除了Ste5表达,并赋予了拉巴胺耐药性.
结论:
- 希斯H2B的Arg95残留物对于招募Spt16至关重要.
- 为了保持STE5的表达,Spt16的招募是必要的.
- 正确的STE5表达,由H2B-Spt16相互作用调节,对于酵母酵母中拉巴胺素诱导的G1细胞周期停止至关重要.
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