Identification and functional characterization of human glycerol-3-phosphate acyltransferase 1 gene promoters

Harada, Nagakatsu; Fujimoto, Erika; Okuyama, Maiko; Sakaue, Hiroshi; Nakaya, Yutaka

doi:10.1016/j.bbrc.2012.05.094

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…Furthermore, DR fed mice and Snell/Ames dwarf mice exhibit altered transcriptional dynamics of peroxisome proliferator-activated receptor α (PPARα) [128], which in turn regulates Srebp1 activity [129,130] and may thus explain the similar expression patterns of lipogenesis genes. Consistently, in both DR and Ames dwarf mice we observed hypermethylation over several Srebf1-target genes (Elovl5, Elovl6, Fasn, Gpam, Acly, Acaca, Aacs) [55,108,112,[131][132][133][134]. Their hypermethylation was further accompanied by transcriptional repression in Ames dwarf mice at young age, which was also observed in young Snell dwarf mice [127].…”

Section: Discussionsupporting

confidence: 79%

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity

et al. 2018

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Dietary, pharmacological and genetic interventions can extend health-and lifespan in diverse mammalian species. DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing, and this is prevented by lifespan-extending interventions. However, whether these interventions also actively shape the epigenome, and whether such epigenetic reprogramming contributes to improved health at old age, remains underexplored. We analysed published, wholegenome, BS-seq data sets from mouse liver to explore DNA methylation patterns in aged mice in response to three lifespan-extending interventions: dietary restriction (DR), reduced TOR signaling (rapamycin), and reduced growth (Ames dwarf mice). Dwarf mice show enhanced DNA hypermethylation in the body of key genes in lipid biosynthesis, cell proliferation and somatotropic signaling, which strongly correlates with the pattern of transcriptional repression. Remarkably, DR causes a similar hypermethylation in lipid biosynthesis genes, while rapamycin treatment increases methylation signatures in genes coding for growth factor and growth hormone receptors. Shared changes of DNA methylation were restricted to hypermethylated regions, and they were not merely a consequence of slowed ageing, thus suggesting an active mechanism driving their formation. By comparing the overlap in ageing-independent hypermethylated patterns between all three interventions, we identified four regions, which, independent of genetic background or gender, may serve as novel biomarkers for longevity-extending interventions. In summary, we identified gene body hypermethylation as a novel and partly conserved signature of lifespan-extending interventions in mouse, highlighting epigenetic reprogramming as a possible intervention to improve health at old age.

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Section: Discussionsupporting

confidence: 79%

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity

et al. 2018

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“…4g). These genes code for several key enzymes of hepatic lipid metabolism including ATP-citrate lyase ( Acly ), Malic enzyme 1 ( Me1 ) [67], acetoacetyl-CoA synthetase ( AACS2 ) [68], pyruvate kinase ( PKLR ) [69], glycerol-3-phosphate acyltransferase ( GPAM ) [70], fatty acid elongase 6 ( Elovl6 ) [71] and acetyl-CoA carboxylase 1 ( ACACA ) [72] (Fig. 4f).…”

Section: Resultsmentioning

confidence: 99%

“…The transcription factor Srebf1 (SREBP1) is a key regulator of lipogenic enzyme expression in the liver [67, 73, 74] and mediates hepatic insulin resistance through inhibition of IRS-2 [102]. Interestingly, we found that the Srebf1 gene itself and key Srebf1 target genes like Acly , Me1 [67], AACS [68], ACACA [72], GPAM [70], and Elovl5 [103] and Elovl6 [71], which catalyze rate-limiting steps in fatty acid synthesis and fatty acid elongation [104], respectively, were hypermethylated and transcriptionally downregulated in response to DR (Fig. 6f, g).…”

Section: Discussionmentioning

confidence: 99%

Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism

et al. 2017

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BackgroundDietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan in diverse species, including rodents. However, the mechanisms by which DR interacts with the aging process to improve health in old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR because it is sensitive to the effects of nutrition and can affect gene expression memory over time.ResultsHere, we profile genome-wide changes in DNA methylation, gene expression and lipidomics in response to DR and aging in female mouse liver. DR is generally strongly protective against age-related changes in DNA methylation. During aging with DR, DNA methylation becomes targeted to gene bodies and is associated with reduced gene expression, particularly of genes involved in lipid metabolism. The lipid profile of the livers of DR mice is correspondingly shifted towards lowered triglyceride content and shorter chain length of triglyceride-associated fatty acids, and these effects become more pronounced with age.ConclusionsOur results indicate that DR remodels genome-wide patterns of DNA methylation so that age-related changes are profoundly delayed, while changes at loci involved in lipid metabolism affect gene expression and the resulting lipid profile.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1187-1) contains supplementary material, which is available to authorized users.

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“…The use of cell type specific promoters allows greater control over the expression of foreign genes. Liver cell specific promoters such as Glycerol-3-Phosphate Acyltransferase (GPAT I and GPAT II) and phosphoglycerate kinase 1 (pgk-1), albumin, human alpha1-antitrypsin and hemopexin are shown to be active in hepatocytes of human and mice origin [7,58,59]. Similarly, viral promoters and vectors have been tested in different cell lines for their specificity and stability of expression.…”

Section: Promoters For Hepatic Cell Linesmentioning

confidence: 99%

“…Similar approaches have been used in hepatoma cells and other higher eukaryotes and mammalian cells and include lipofection, DEAE-dextran, calcium-phosphate, viral vectors, peptides and electroporation [6]. Lipofection has been used to achieve transient as well as steady transfection in hepatoma cells resulting in an improved and stable expression of transgenes even after several passages [7]. To develop protocols for cell type specific reporter activity, we discuss the use of alternate promoters and vectors for stable expression in actively dividing cells.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in live cell imaging of hepatoma cells

2014

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Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example.

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Identification and functional characterization of human glycerol-3-phosphate acyltransferase 1 gene promoters

Cited by 9 publications

References 24 publications

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity

Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism

Recent advances in live cell imaging of hepatoma cells

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