Zinc finger 4 negatively controls the transcriptional activator Fzf1 in Saccharomyces cerevisiae.

IF 4.5 Q1 MICROBIOLOGY
mLife Pub Date : 2024-09-23 eCollection Date: 2024-09-01 DOI:10.1002/mlf2.12141
Ying Du, Chaoqun Ma, Stanley A Moore, Wei Xiao
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引用次数: 0

Abstract

Fzf1 is a Saccharomyces cerevisiae transcription factor containing five zinc fingers (ZFs). It regulates the expression of at least five downstream genes, including SSU1, YHB1, DDI2/3, and YNR064c, by recognizing a consensus sequence, CS2, found in these gene promoters. These gene products are involved in cellular responses to various chemical stresses. For example, SSU1 encodes a sodium sulfite efflux protein that confers sulfite resistance. However, the underlying molecular mechanism through which Fzf1 responds to chemical stress and coordinates target gene activation remains elusive. Interestingly, several mutations in the fourth ZF (ZF4) of Fzf1 have previously been reported to confer either sulfite resistance or elevated basal-level expression of YHB1, indicating that ZF4 negatively impacts Fzf1 activity. Since ZF4 is dispensable for CS2 binding in vitro, we hypothesized that ZF4 is a negative regulator of Fzf1 and that chemically induced Fzf1-regulated gene expression occurs via de-repression. All five genes examined were cross-induced by corresponding chemicals in an Fzf1-dependent manner, and all three ZF4 mutations and a ZF4 deletion conferred increased basal-level expression and SSU1-dependent sulfite resistance. A ZF4 deletion did not alter the target DNA binding, consistent with the observed codominant phenotype. These observations collectively reveal that Fzf1 remains inactive by default at the target promoters and that its activation is at least partially achieved by self-derepression through chemical modification and/or a conformational change.

锌指 4 负向控制酿酒酵母中的转录激活因子 Fzf1。
Fzf1 是一种含有五个锌指(ZF)的酿酒酵母转录因子。它通过识别 SSU1、YHB1、DDI2/3 和 YNR064c 等基因启动子中的共识序列 CS2,调节至少五个下游基因的表达。这些基因产物参与细胞对各种化学胁迫的反应。例如,SSU1 编码亚硫酸钠外排蛋白,可赋予亚硫酸盐抗性。然而,Fzf1 对化学胁迫做出反应并协调靶基因激活的基本分子机制仍未确定。有趣的是,此前有报道称,Fzf1 的第四个 ZF(ZF4)中的几个突变可赋予亚硫酸盐抗性或 YHB1 基础水平表达的升高,这表明 ZF4 对 Fzf1 的活性有负面影响。由于 ZF4 在体外与 CS2 结合是不可或缺的,我们假设 ZF4 是 Fzf1 的负调控因子,化学诱导的 Fzf1 调控基因表达是通过去抑制发生的。所检测的五个基因都以 Fzf1 依赖性方式被相应的化学物质交叉诱导,所有三个 ZF4 突变和一个 ZF4 缺失都会增加基础水平的表达和 SSU1 依赖性亚硫酸盐抗性。ZF4 缺失不会改变目标 DNA 结合,这与观察到的共显性表型一致。这些观察结果共同揭示了 Fzf1 在靶启动子上默认保持非活性,其激活至少部分是通过化学修饰和/或构象变化的自我抑制实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.30
自引率
0.00%
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