Characterization of Rat Liver-specific Methionine Adenosyltransferase Gene Promoter

Álvarez, Luis; Sánchez-Góngora, Estrella; Mingorance, Jesús; Pajares, Marı́a A.; Mato, José M.

doi:10.1074/jbc.272.36.22875

Cited by 26 publications

(24 citation statements)

References 56 publications

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“…Five micrograms of the ␤-galactosidase expression vector pCH110 (Amersham Pharmacia Biotech) was included as an internal standard of transfection efficiency. After 24 hr, cells were harvested and luciferase and galactosidase activities were determined as described [33]. Values reported are means of three independent experiments performed in triplicate.…”

Section: Transient Transfections Of Cultured Rat Hepatocytesmentioning

confidence: 99%

“…Cells were transfected with 5 g of a MAT1A promoter-luciferase construct encompassing 1.4 kb of the 5Ј-flanking region of this gene (nucleotides Ϫ1405 to ϩ65) [33], using the TFx50 reagent (Promega) according to the manufacturer's instructions. Five micrograms of the ␤-galactosidase expression vector pCH110 (Amersham Pharmacia Biotech) was included as an internal standard of transfection efficiency.…”

Section: Transient Transfections Of Cultured Rat Hepatocytesmentioning

confidence: 99%

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Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine

Carretero

Latasa

Garcı́a-Trevijano

et al. 2001

Biochemical Pharmacology

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Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological conditions such as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon neoplastic transformation of the liver. In the present work, we evaluated whether MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3-methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA levels were reduced by 50% following in vivo administration of 3-MC to adult male rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time-and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter construct transfected into rat hepatocytes, but MAT1A mRNA stability was not affected. We recently showed that liver MAT1A expression is induced by AdoMet in cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented the negative effects of 3-MC on MAT1A expression. Taken together, our data demonstrate that liver MAT1A gene expression is targeted by PAHs, independently of AhR activation. The effect of AdoMet may be part of the protective action of this molecule in liver damage.

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Section: Transient Transfections Of Cultured Rat Hepatocytesmentioning

confidence: 99%

Section: Transient Transfections Of Cultured Rat Hepatocytesmentioning

confidence: 99%

Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine

Carretero

Latasa

Garcı́a-Trevijano

et al. 2001

Biochemical Pharmacology

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“…Our ®nding of MAT1A being hypomethylated in the liver contributes to the understanding of the tissue-restricted expression of this gene. Additionally, this situation may explain why the MAT1A promoter was able to drive reporter gene expression upon transient transfection not only in liver type cells such as the rat hepatoma H35, but also in the non-hepatic CHO cells, in which the endogenous MAT1A gene is silenced [8].…”

Section: Resultsmentioning

confidence: 99%

“…Rat MAT1A and MAT2A promoters have been cloned, sequenced, and functionally characterized [8,9]. However the mechanisms responsible for the tissue-speci®c expression of these two genes cannot be completely explained by the presence of cell-type-speci®c promoter elements, or by the action of tissue-speci®c transcription factors [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…However the mechanisms responsible for the tissue-speci®c expression of these two genes cannot be completely explained by the presence of cell-type-speci®c promoter elements, or by the action of tissue-speci®c transcription factors [8,9]. An additional level of information, which can inuence gene expression is conveyed by DNA methylation at CpG sites [10±12].…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Torres

López-Rodas

Latasa

et al. 2000

The International Journal of Biochemistry & Cell Biology

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Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet). In mammals MAT activity derives from two separate genes which display a tissue-speci®c pattern of expression. While MAT1A is expressed only in the adult liver, MAT2A is expressed in non-hepatic tissues. The mechanisms behind the selective expression of these two genes are not fully understood. In the present report we have evaluated MAT1A and MAT2A methylation in liver and in other tissues, such as kidney, by methylationsensitive restriction enzyme digestion of genomic DNA. Our data indicate that MAT1A is hypomethylated in liver and hypermethylated in non-expressing tissues. The opposite situation is found for MAT2A. Additionally, histones associated to MAT1A and MAT2A genes showed enhanced levels of acetylation in expressing tissues (two-fold for MAT1A and 3.5-fold for MAT2A liver and kidney respectively). These observations support a role for chromatin structure and its modi®cation in the tissue-speci®c expression of both MAT genes. #

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Methionine Adenosyltransferase (S‐Adenosylmethionine Synthetase)

Pajares

Markham

2011

Advances in Enzymology - And Related Areas of Molecular Biology

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10.3. Thermal Unfolding 10.4. Association of MAT III to form MAT I: Role of the Disulfide C35-C61 10.5. Complementary Folding Data Obtained in MAT Proteins of Different Origins 11. MAT Inhibitors 12. Role of MAT in Diseases 12.1. Cognitive and Neurodegenerative Diseases 12.2. Human Mutations in MAT1A Gene: Hypermethioninemia and Demyelination 12.3. MAT and Cancer 12.4. MAT and Ethanol 2. MAMMALIAN MATs Early studies on mammalian MATs showed the existence of this activity in all the tissues studied, the highest being observed in liver. However, complex kinetics were obtained which made the results difficult to interpret until the presence of several isoenzymes was realized. Separations carried out on phenyl Sepharose columns showed elution of three peaks with different hydrophobic character; these were named according to the order of elution as MAT I, II and III. All these isoenzymes share some characteristics such as the Mg 2+ dependence of their 9/14/2012 Page 6 of 80 activity (S 0.5 !1 mM), stimulation by K + ions, and their AdoMet-inducible tripolyphosphatase activity [4, 5]. 2.1. MAT I/III isoenzymes Since their discovery, these isoenzymes were known as liver-specific forms of MAT, until Lu et al. in 2003 [6] showed their presence also in pancreas. Several laboratories have reported in depth studies of MAT I and III which have been carried out using adult liver. The differences can be summarized as follows: i) MAT I is a tetramer whereas MAT III is a dimer, with respective Mr appearing as 200 and 110 kDa upon gel filtration chromatography, ii) their Km values for methionine are in the micromolar range for MAT I (60-120 µM) and in the millimolar range for MAT III (1 mM) [7, 8]; iii) MAT III can be activated by DMSO at physiological concentrations of methionine (60 µM) and is highly hydrophobic (eluting from phenyl Sepharose columns at 50% DMSO (v/v)); and, iv) AdoMet inhibits MAT I and activates MAT III. Some of these differences are normally used to distinguish between isoenzymes in activity assays. Both purified proteins show a common single band (designated "1) of approximately 48 kDa on SDS-PAGE, and antibodies raised against the dimer form recognized both, thus suggesting that a single type of subunit arranged in two assemblies could explain the presence of both oligomers [7]. Further experiments that supported this hypothesis included peptide mapping of the purified isoenzymes [7], dissociation of the tetramer to the dimer using LiBr [9] or N-ethylmaleimide (NEM) modification [10]. The final confirmation came upon cloning of a single cDNA [11, 12] followed by overexpresion in E. coli cells [13], which showed in vivo production of dimers and tetramers. This single subunit type is a product of the MAT1A gene that contains nine exons and eight introns spanning !20 kb [14], and has been localized by fluorescence in situ hybridization to the human chromosome 10q.22 [15]. Animal models, as well as the analysis of human samples, led to the identification of changes in the MAT I/III ratio in pathological conditi...

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Characterization of Rat Liver-specific Methionine Adenosyltransferase Gene Promoter

Cited by 26 publications

References 56 publications

Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine

Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine

DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Methionine Adenosyltransferase (S‐Adenosylmethionine Synthetase)

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