Analysis of gene network regulating yeast multidrug resistance by artificial activation of transcription factors: involvement of Pdr3 in salt tolerance

Analysis of gene network regulating yeast multidrug resistance by artificial activation of transcription factors: involvement of Pdr3 in salt tolerance
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DOI:
10.1016/j.gene.2004.02.003
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发表时间:
2004-05-12
期刊:
影响因子:
3.5
通讯作者:
Ito, T
Ito, T
中科院分区:
生物学3区
文献类型:
--
作者:
Onda, M;Ota, K;Ito, T

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我们建立了一个策略,组成性激活Zn(2)Cys(6)型蛋白的DNA结合域与VP16反式激活域融合。为了探索调控酵母多药耐药性的基因网络,将该策略应用于已知调控多药耐药性的Pdr1、Pdr3和Yrr1。以及三种未鉴定的Yrr1相关转录因子。DNA微阵列分析显示,所有6个突变体诱导典型的药物转运蛋白基因,包括SNQ 2和YOR 1,表明调控冗余。另一方面,每个显示一个独特的频谱的目标,这是一致的系统发育树的转录因子,大概反映了他们的功能规范。事实上,对每个转录因子特异性靶基因的仔细分析使我们揭示了Pdr3在耐盐性中的意想不到的作用。因此,该策略不仅有助于识别靶基因,而且有助于揭示复杂基因调控网络中的冗余性和特异性。(C)2004 Elsevier B.V.保留所有权利。
We established a strategy to constitutively activate Zn(2)Cys(6)-type protein by fusing its DNA-binding domain with the VP16 transactivation domain. To explore gene network regulating yeast multidrug resistance, the strategy was applied to Pdr1, Pdr3 and Yrr1, known to regulate multidrug resistance. as well as three uncharacterized Yrr1-related transcription factors. DNA microarray analysis revealed that all of the six mutants induce typical drug transporter genes including SNQ2 and YOR1, suggesting redundancy in regulation. On the other hand, each displays a unique spectrum of targets, which is coincident with the phylogenetic tree of the transcription factors and presumably reflects their functional specification. Indeed, careful analysis of target genes specific to each transcription factor led us to reveal an unexpected role for Pdr3 in salt tolerance. The strategy would thus contribute not only to identify target genes but to reveal redundancy and specificity in complex gene regulatory networks. (C) 2004 Elsevier B.V. All rights reserved.