Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays

Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays
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DOI:
10.1074/jbc.m005946200
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发表时间:
2000-10-13
影响因子:
4.8
通讯作者:
Winge, DR
Winge, DR
中科院分区:
生物学2区
文献类型:
--
作者:
Gross, C;Kelleher, M;Winge, DR

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在酿酒酵母中,铜离子通过两种转录激活因子Ace 1和Mad调节基因表达。Ace 1介导暴露于铜盐应激水平的细胞中铜诱导的基因表达,而Mad在铜缺乏条件下激活一组基因。DNA微阵列杂交实验揭示了一组有限的酵母基因差异表达的生长条件下,过量的铜或铜缺乏。疯狂激活了六个S的表达。最后三个新鉴定的Mad靶基因中的两个没有已知的功能;第三个,YFR 055 w,与由CYS 3编码的胱硫醚γ-裂解酶同源。在含有组成型活性Mad的细胞中差异表达的几个基因,命名为Mac 1(up 1),不是Mad的直接靶点。这些基因的诱导或抑制可能是由于组成性Mad活性的细胞的继发效应。铜水平升高诱导金属硫蛋白CUP 1和CRS 5以及铁摄取系统中的两个基因FET 3和FTR 1的表达。铜诱导的FET 3和FTR 1表达源于铜对细胞铁池的间接影响。
In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mad. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mad activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mad activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w, Two of the last three newly identified Mad target genes have no known function; the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mad, designated Mac1(up1), are not direct targets of Mad. Induction or repression of these genes is likely a secondary effect of cells because of constitutive Mad activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5 and two genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 expression arises from an indirect copper effect on cellular iron pools.