需要重叠的协同激活器功能,才能通过Candida glabrata Pdr1转录因子进行转录激活
bioRxiv : the preprint server for biology
|June 10, 2024
概括
在Pdr1中获得功能的突变驱动了Candida glabrata中的醇耐药性. 共激活体复合体SWI/SNF和SAGA对于抗性基因的Pdr1-介导转录至关重要.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 在 *Candida glabrata* 中的亚醇耐药性是一个日益严重的临床问题.
- 这种抗性通常与转录因子Pdr1的突变有关,导致像*CDR1*这样的基因过度表达.
- 突变的Pdr1增强目标基因转录的确切机制尚不清楚.
研究的目的:
- 为了识别与野生类型和突变的Pdr1.1相互作用的协作激活蛋白.
- 阐明这些联合激活剂在Pdr1-依赖基因转录和醇耐药性中的作用.
主要方法:
- Pdr1的并联亲和净化 (TAP) 来识别相互作用的蛋白质.
- 构建和分析共激活基因 (*SNF2*, *SPT7*) 的删除突变.
- 使用条件降解系统来急性耗尽协活性剂.
主要成果:
- 确定了Snf2 (SWI/SNF复合体) 和Spt7/Ngg1 (SAGA复合体) 作为Pdr1的协同激活剂.
- 删除*SNF2*或*SPT7*导致生长缺陷.
- SWI/SNF或SAGA急性耗尽损害了Pdr1依赖转录;联合耗尽严重影响了*PDR1*自我调节.
结论:
- SWI/SNF和SAGA复合体是Pdr1功能的关键联合激活剂.
- 这些复合体共同推动Pdr1-调节基因的高水平转录,包括赋予醇耐药性的基因.
- 了解这些机制可以为打击*Candida glabrata*抗真菌耐药性的策略提供信息.
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