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Reference - PMID:24003116 - Zinc finger protein Loz1 is required for zinc-responsive regulation of gene expression in fission yeast.

Reference summary

PubMed ID
PMID:24003116
Title
Zinc finger protein Loz1 is required for zinc-responsive regulation of gene expression in fission yeast.
Authors
Corkins ME, May M, Ehrensberger KM, Hu YM, Liu YH, Bloor SD, Jenkins B, Runge KW, Bird AJ
Citation
Proc Natl Acad Sci U S A 2013 Sep 17;110(38):15371-6
Publication year
2013
Abstract
In Schizosaccharomyces pombe, alcohol dehydrogenase 1 (Adh1) is an abundant zinc-requiring enzyme that catalyses the conversion of acetaldehyde to ethanol during fermentation. In a zinc-replete cell, adh1 is highly expressed. However, in zinc-limited cells, adh1 gene expression is repressed, and cells induce the expression of an alternative alcohol dehydrogenase encoded by the adh4 gene. In our studies examining this zinc-dependent switch in alcohol dehydrogenase gene expression, we isolated an adh1Δ strain containing a partial loss of function mutation that resulted in higher levels of adh4 transcripts in zinc-replete cells. This mutation also led to the aberrant expression of other genes that are typically regulated by zinc. Using linkage analysis, we have mapped the position of this mutation to a single gene called Loss Of Zinc sensing 1 (loz1). Loz1 is a 55-kDa protein that contains a double C2H2-type zinc finger domain. The mapped mutation that disrupts Loz1 function leads to an arginine to glycine substitution in the second zinc finger domain, suggesting that the double zinc finger domain is important for Loz1 function. We show that loz1Δ cells hyperaccumulate zinc and that Loz1 is required for gene repression in zinc-replete cells. We also have found that Loz1 negatively autoregulates its own expression. We propose that Loz1 is a unique metalloregulatory factor that plays a central role in zinc homeostasis in S. pombe.

Annotation

GO biological process

GO:0006882 - intracellular zinc ion homeostasis

Genes:

GO:0000122 - negative regulation of transcription by RNA polymerase II

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GO cellular component

GO:0005634 - nucleus

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GO molecular function

GO:0001227 - DNA-binding transcription repressor activity, RNA polymerase II-specific

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GO:0000978 - RNA polymerase II cis-regulatory region sequence-specific DNA binding

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Qualitative gene expression

PomGeneEx:0000012 - RNA level decreased

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Single locus phenotype

FYPO:0002003 - abolished RNA polymerase II proximal promoter sequence-specific DNA binding

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Genotypes:

FYPO:0001534 - decreased cellular zinc level

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Genotypes:

FYPO:0003008 - decreased repression of transcription during cellular response to zinc

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Genotypes:

FYPO:0001117 - decreased RNA level during vegetative growth

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Genotypes:

FYPO:0001552 - increased cellular zinc level

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Genotypes:

FYPO:0000825 - increased RNA level during vegetative growth

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Genotypes:

Warnings

PBO:0000070 - gene structure updated

Genes: