The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression.

Heuchel, Rainer; Radtke, Freddy; Georgiev, Oleg; Stark, Gerlinde; Aguet, Michel; Schaffner, Walter

doi:10.1002/j.1460-2075.1994.tb06581.x

Cited by 455 publications

(410 citation statements)

References 27 publications

Supporting

Mentioning

388

Contrasting

Unclassified

Order By: Relevance

“…Human MTF-1 is able to rescue the sensitivity of dMTF-1 mutants to both high and low copper concentrations Both mammalian and Drosophila MTF-1 have been shown to be essential for an efficient response to heavy metal load (Radtke et al, 1993;Heuchel et al, 1994;Egli et al, 2003). However, there is only a limited similarity between the two transcription factors outside of the zinc finger region ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Balamurugan

Egli²,

Selvaraj³

et al. 2004

Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The zinc finger transcription factor MTF-1 (metal-responsive transcription factor-1) is conserved from insects to vertebrates. Its major role in both organisms is to control the transcription of genes involved in the homeostasis and detoxification of heavy metal ions such as Cu 2q , Zn 2q and Cd 2q . In mammals, MTF-1 serves at least two additional roles. First, targeted disruption of the MTF-1 gene results in death at embryonic day 14 due to liver degeneration, revealing a stage-specific developmental role. Second, under hypoxic-anoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PlGF), an angiogenic protein. Recently we characterized dMTF-1, the Drosophila homolog of mammalian MTF-1. Here we present a series of studies to compare the metal response in mammals and insects, which reveal common features but also differences. A human MTF-1 transgene can restore to a large extent metal tolerance to flies lacking their own MTF-1 gene, both at low and high copper concentrations. Likewise, Drosophila MTF-1 can substitute for human MTF-1 in mammalian cell culture, although both the basal and the metal-induced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothionein-type promoters respond poorly, if at all, to Hg 2q in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.

show abstract

Section: Resultsmentioning

confidence: 99%

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Balamurugan

Egli²,

Selvaraj³

et al. 2004

Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Twelve overrepresented transcription factor binding sites were present within the promoter regions of Mt1 and Mt2 (Table 1). These binding sites were associated with many trans-acting elements, but only few of these had previously been linked to Mt1 and Mt2 regulation, including signal transducer and activator of transcription factors 1 and 3 (Stat1 and Stat3) (Lee et al, 1999) and metal activated transcription factor 1 (Mtf1) (Heuchel et al, 1994).…”

Section: Co-expression Of Cr-regulated Genesmentioning

confidence: 99%

Genes regulated by caloric restriction have unique roles within transcriptional networks

Swindell

2008

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

Caloric restriction (CR) has received much interest as an intervention that delays age-related disease and increases lifespan. Whole-genome microarrays have been used to identify specific genes underlying these effects, and in mice, this has led to the identification of genes with expression responses to CR that are shared across multiple tissue types. Such CR-regulated genes represent strong candidates for future investigation, but have been understood only as a list, without regard to their broader role within transcriptional networks. In this study, co-expression and network properties of CR-regulated genes were investigated using data generated by more than 600 Affymetrix microarrays. This analysis identified groups of co-expressed genes and regulatory factors associated with the mammalian CR response, and uncovered surprising network properties of CR-regulated genes. Genes downregulated by CR were highly connected and located in dense network regions. In contrast, CR-upregulated genes were weakly connected and positioned in sparse network regions. Some network properties were mirrored by CR-regulated genes from invertebrate models, suggesting an evolutionary basis for the observed patterns. These findings contribute to a systems-level picture of how CR influences transcription within mammalian cells, and point towards a comprehensive understanding of CR in terms of its influence on biological networks.

show abstract

“…The mouse metallothionein-I reporter promoter used has been described by Radtke et al (1993). The human MTF-1 expression vector is described in Heuchel et al (1994).…”

Section: Construction Of Dna Templates and Expression Vectorsmentioning

confidence: 99%

“…We have sequenced and characterized the complete Fugu ortholog of the metal regulatory transcription factor MTF-1, a zinc finger protein that was originally characterized in the mouse (Westin and Schaffner, 1988;Radtke et al, 1993;Labbé et al, 1993;Heuchel et al, 1994;Otsuka et al, 1994;Palmiter, 1994;Dalton et al, 1996;Bittel et al, 1998;Günes et al, 1998). MTF-1 activates transcription in response to heavy metal load by binding to short DNA sequence motifs, so-called metal responsive elements (MREs).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Transcription Factor MTF-1 from the Japanese Pufferfish (<I>Fugu rubripes</I>) Reveals Evolutionary Conservation of Heavy Metal Stress Response

Maur¹,

Belser²,

Elgar³

et al. 1999

Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The pufferfish Fugu rubripes was recently introduced as a new model organism for genomic studies, since it contains a full set of vertebrate genes but only 13% as much DNA as a mammal. Fugu genes tend to be smaller and densely spaced due to shortening of introns and intergenic spacers. We isolated the Fugu gene for the metal-responsive transcription factor MTF-1 (MTF1), a mediator of heavy metal regulation and oxidative stress response previously characterized in mammals. In addition, most of the cDNA sequence was also determined. The 780 amino acid MTF-1 protein of Fugu is very similar to that of mouse and human, with 90% amino acid identity in the DNA binding zinc finger domain and 57% overall identity. Expression of the pufferfish cDNA in mammalian cells shows that Fugu MTF-1 has the same DNA binding specificity as its mammalian counterpart and also induces transcription in response to zinc and cadmium. The proteincoding part of the Fugu MTF-1 gene spans 6.4 kb and consists of 11 exons. Upstream region and first exon constitute a CpG island. The distance between stop codon and polyadenylation motifs is Ͼ 2 kb, suggesting a very long 3 untranslated mRNA region, followed by another CpG island which may represent the promoter of the next gene downstream. Part of the MTF-1 genomic structure was also determined in the mouse, and some striking similarities were found: for example, the upstream adjacent gene in both species is INPP5P, encoding a phosphatase. The mouse MTF-1 promoter is also embedded in a CpG island, which however shares no sequence similarity to the one of Fugu. The Fugu CpG island is shorter than the one of the mouse and has no elevated [G+C] content; these and other data indicate that CpG islands of fish may represent a primordial stage of CpG island evolution.

show abstract

The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression.

Cited by 455 publications

References 27 publications

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Genes regulated by caloric restriction have unique roles within transcriptional networks

Characterization of the Transcription Factor MTF-1 from the Japanese Pufferfish (<I>Fugu rubripes</I>) Reveals Evolutionary Conservation of Heavy Metal Stress Response

Contact Info

Product

Resources

About