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Rapid transcriptional autoregulation of a yeast metalloregulatory transcription factor is essential for high-level copper detoxification.

Identifieur interne : 002C03 ( Main/Exploration ); précédent : 002C02; suivant : 002C04

Rapid transcriptional autoregulation of a yeast metalloregulatory transcription factor is essential for high-level copper detoxification.

Auteurs : P. Zhou ; D J Thiele

Source :

RBID : pubmed:8370529

Descripteurs français

English descriptors

Abstract

Copper detoxification in the yeast Candida glabrata is carried out in large part by a family of metallothionein (MT) genes: a unique MT-I gene, a tandemly amplified MT-IIa gene, and a single unlinked MT-IIb gene. In response to elevated environmental copper levels, members of this MT gene family are transcriptionally activated by a copper-dependent, sequence-specific DNA-binding transcription factor, AMT1. AMT1 shares several structural and functional features with the Saccharomyces cerevisiae copper metalloregulatory transcription factor ACE1, which is constitutively expressed and poised for rapid transcriptional responses to the toxic metal copper. In this paper, we demonstrate that AMT1 is subject to positive transcriptional autoregulation, which is exerted through binding of copper-activated AMT1 to a single copper responsive element in the AMT1 promoter. A nonautoregulatory amt1 mutant displayed a marked decrease in both copper tolerance and expression of the MT-II genes, which are critical for high-level copper detoxification in Candida glabrata. Kinetic analysis demonstrated the remarkably rapid AMT1 mRNA accumulation in the presence of copper, which is followed by increased expression of the metallothionein gene products. These results demonstrate that AMT1-positive autoregulation plays a critical role in metal detoxification and suggest that the rapid autoactivation of the AMT1 metalloregulatory transcription factor biosynthesis is essential for C. glabrata to quickly build up a cellular defense line to protect cells upon exposure to high environmental copper levels.

DOI: 10.1101/gad.7.9.1824
PubMed: 8370529


Affiliations:


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Le document en format XML

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<name sortKey="Zhou, P" sort="Zhou, P" uniqKey="Zhou P" first="P" last="Zhou">P. Zhou</name>
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<nlm:affiliation>Department of Biological Chemistry, University of Michigan School, Ann Arbor 48109-0606.</nlm:affiliation>
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<term>Base Sequence (MeSH)</term>
<term>Binding Sites (MeSH)</term>
<term>Candida (genetics)</term>
<term>Candida (metabolism)</term>
<term>Copper (metabolism)</term>
<term>DNA, Recombinant (MeSH)</term>
<term>DNA-Binding Proteins (genetics)</term>
<term>DNA-Binding Proteins (metabolism)</term>
<term>Fungal Proteins (MeSH)</term>
<term>Gene Expression Regulation, Fungal (MeSH)</term>
<term>Homeostasis (MeSH)</term>
<term>Kinetics (MeSH)</term>
<term>Metallothionein (genetics)</term>
<term>Metallothionein (metabolism)</term>
<term>Molecular Sequence Data (MeSH)</term>
<term>Promoter Regions, Genetic (MeSH)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Transcription Factors (genetics)</term>
<term>Transcription Factors (metabolism)</term>
<term>Transcription, Genetic (MeSH)</term>
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<term>ADN recombiné (MeSH)</term>
<term>ARN messager (métabolisme)</term>
<term>Candida (génétique)</term>
<term>Candida (métabolisme)</term>
<term>Cinétique (MeSH)</term>
<term>Cuivre (métabolisme)</term>
<term>Données de séquences moléculaires (MeSH)</term>
<term>Facteurs de transcription (génétique)</term>
<term>Facteurs de transcription (métabolisme)</term>
<term>Homéostasie (MeSH)</term>
<term>Métallothionéine (génétique)</term>
<term>Métallothionéine (métabolisme)</term>
<term>Protéines de liaison à l'ADN (génétique)</term>
<term>Protéines de liaison à l'ADN (métabolisme)</term>
<term>Protéines fongiques (MeSH)</term>
<term>Régions promotrices (génétique) (MeSH)</term>
<term>Régulation de l'expression des gènes fongiques (MeSH)</term>
<term>Sites de fixation (MeSH)</term>
<term>Séquence nucléotidique (MeSH)</term>
<term>Transcription génétique (MeSH)</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>DNA-Binding Proteins</term>
<term>Metallothionein</term>
<term>Transcription Factors</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Copper</term>
<term>DNA-Binding Proteins</term>
<term>Metallothionein</term>
<term>RNA, Messenger</term>
<term>Transcription Factors</term>
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<term>Candida</term>
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<term>Candida</term>
<term>Facteurs de transcription</term>
<term>Métallothionéine</term>
<term>Protéines de liaison à l'ADN</term>
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<term>Candida</term>
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<term>ARN messager</term>
<term>Candida</term>
<term>Cuivre</term>
<term>Facteurs de transcription</term>
<term>Métallothionéine</term>
<term>Protéines de liaison à l'ADN</term>
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<term>Base Sequence</term>
<term>Binding Sites</term>
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<term>Fungal Proteins</term>
<term>Gene Expression Regulation, Fungal</term>
<term>Homeostasis</term>
<term>Kinetics</term>
<term>Molecular Sequence Data</term>
<term>Promoter Regions, Genetic</term>
<term>Transcription, Genetic</term>
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<term>Cinétique</term>
<term>Données de séquences moléculaires</term>
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<term>Régions promotrices (génétique)</term>
<term>Régulation de l'expression des gènes fongiques</term>
<term>Sites de fixation</term>
<term>Séquence nucléotidique</term>
<term>Transcription génétique</term>
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<div type="abstract" xml:lang="en">Copper detoxification in the yeast Candida glabrata is carried out in large part by a family of metallothionein (MT) genes: a unique MT-I gene, a tandemly amplified MT-IIa gene, and a single unlinked MT-IIb gene. In response to elevated environmental copper levels, members of this MT gene family are transcriptionally activated by a copper-dependent, sequence-specific DNA-binding transcription factor, AMT1. AMT1 shares several structural and functional features with the Saccharomyces cerevisiae copper metalloregulatory transcription factor ACE1, which is constitutively expressed and poised for rapid transcriptional responses to the toxic metal copper. In this paper, we demonstrate that AMT1 is subject to positive transcriptional autoregulation, which is exerted through binding of copper-activated AMT1 to a single copper responsive element in the AMT1 promoter. A nonautoregulatory amt1 mutant displayed a marked decrease in both copper tolerance and expression of the MT-II genes, which are critical for high-level copper detoxification in Candida glabrata. Kinetic analysis demonstrated the remarkably rapid AMT1 mRNA accumulation in the presence of copper, which is followed by increased expression of the metallothionein gene products. These results demonstrate that AMT1-positive autoregulation plays a critical role in metal detoxification and suggest that the rapid autoactivation of the AMT1 metalloregulatory transcription factor biosynthesis is essential for C. glabrata to quickly build up a cellular defense line to protect cells upon exposure to high environmental copper levels.</div>
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<AbstractText>Copper detoxification in the yeast Candida glabrata is carried out in large part by a family of metallothionein (MT) genes: a unique MT-I gene, a tandemly amplified MT-IIa gene, and a single unlinked MT-IIb gene. In response to elevated environmental copper levels, members of this MT gene family are transcriptionally activated by a copper-dependent, sequence-specific DNA-binding transcription factor, AMT1. AMT1 shares several structural and functional features with the Saccharomyces cerevisiae copper metalloregulatory transcription factor ACE1, which is constitutively expressed and poised for rapid transcriptional responses to the toxic metal copper. In this paper, we demonstrate that AMT1 is subject to positive transcriptional autoregulation, which is exerted through binding of copper-activated AMT1 to a single copper responsive element in the AMT1 promoter. A nonautoregulatory amt1 mutant displayed a marked decrease in both copper tolerance and expression of the MT-II genes, which are critical for high-level copper detoxification in Candida glabrata. Kinetic analysis demonstrated the remarkably rapid AMT1 mRNA accumulation in the presence of copper, which is followed by increased expression of the metallothionein gene products. These results demonstrate that AMT1-positive autoregulation plays a critical role in metal detoxification and suggest that the rapid autoactivation of the AMT1 metalloregulatory transcription factor biosynthesis is essential for C. glabrata to quickly build up a cellular defense line to protect cells upon exposure to high environmental copper levels.</AbstractText>
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