依赖于Rtf1/Prf1的组素修饰轴可以抵消裂变酵母中的多药性耐药性
Jennifer J Chen1, Calvin Moy1, Viviane Pagé1
1Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Life science alliance
|March 21, 2024
概括
在裂变酵母中研究RNA聚合酶II转录延长发现,在真菌药物耐受性中,Rtf1-H2Bub1-H3K4me轴和Rpb1 C终端域的共同基因调控作用在真菌药物耐受性中.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 单核细胞转录 单核细胞转录
背景情况:
- RNA聚合酶II转录延长涉及诸如H2B单双化和H3K4甲基化之类的基因组修饰.
- Rtf1延长因子启动了一个调节级联,影响这些组素修饰.
- 这个轴在基因表达和细胞表型中的确切作用仍然不清楚.
研究的目的:
- 研究Rtf1-H2Bub1-H3K4me轴在基因调节中的功能意义.
- 探索这个轴与Schizosaccharomyces pombe*中的耐药性表型之间的联系.
- 为了确定RNA聚合酶II C-终端重复域共享调控功能的突变.
主要方法:
- 使用 * Schizosaccharomyces pombe * 作为一个模型真核生物.
- 引入了影响Rtf1-H2Bub1-H3K4me轴和RNA聚合酶II C端重复域的突变.
- 评估的表型包括氨酸 (HU) 耐药性,dNTP池动态,S相检查点反应和转录对HU的反应.
- 测试了阿佐尔抗真菌剂的敏感性.
主要成果:
- 在Rtf1-H2Bub1-H3K4me轴中的突变赋予了对基尿素 (HU) 的耐药性.
- HU抵抗与改变的dNTP池相关,减少了S相检查点的依赖,以及对HU的转录反应变得.
- 在Rpb1的C端重复域中的突变模仿了这些HU抵抗表型.
- 所有研究的突变物体都对醇抗真菌剂表现出交叉耐药性.
结论:
- Rtf1-H2Bub1-H3K4me轴和Rpb1 C终端重复域共享一个基因调节功能.
- 这种共享功能对于控制真菌耐药性至关重要.
- 这些发现揭示了转录延长机制与抗真菌药物耐药性之间的新联系.
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