Hypomethylation of CpG Sites and <i>c‐myc</i> Gene Overexpression in Hepatocellular Carcinomas, but Not Hyperplastic Nodules, Induced by a Choline‐deficient L‐Amino Acid‐defined Diet in Rats

Tsujiuchi, Toshifumi; Tsutsumi, Masahiro; Sasaki, Yasutaka; Takahama, Makoto; Konishi, Yoichi

doi:10.1111/j.1349-7006.1999.tb00834.x

Cited by 91 publications

(65 citation statements)

References 21 publications

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“…The genes studied herein were differentially expressed in clones when compared with controls, and their expression has been reported to be regulated by DNA methylation at their promoter regions in rats and humans (Tsujiuchi et al, 1999;Yeh et al, 2005). It cannot be excluded that, in contrast to cloned cows, the cloned donor genome of pigs undergoes typical demethylation processes, the patterns of which are similar to their counterparts (Kang et al, 2001).…”

Section: Park Et Almentioning

confidence: 73%

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Park

Lai²,

Samuel³

et al. 2011

Cellular Reprogramming

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Although numerous mammalian species have been successfully cloned by somatic cell nuclear transfer (SCNT), little is known about gene expression of cloned pigs by SCNT. In the present study, expression profiles of 1-month-old cloned pigs generated from fetal fibroblasts (n ¼ 5) were compared to those of age-matched controls (n ¼ 5) using a 13K oligonucleotide microarray. The brain, kidney, and lung were chosen for microarray analysis to represent tissues from endoderm, mesoderm, and ectoderm in origin. In clones, 179 and 154 genes were differentially expressed in the kidney and the lung, respectively (fold change >2, p < 0.05, false discovery rate ¼ 0.05), whereas only seven genes were differentially expressed in the brain of clones. Functional analysis of the differentially expressed genes revealed that they were enriched in diabetic nephropathy in the kidney, delayed alveologenesis as well as downregulated MAPK signaling pathways in the lung, which was accompanied with collapsed alveoli in the histological examination of the lung. To evaluate whether the gene expression anomalies are associated with changes in DNA methylation, global concentration of the methylated cytosine was measured in lung DNA by HPLC. Clones were significantly hypermethylated (5.72%) compared to the controls (4.13%). Bisulfite-pyrosequencing analyses of the promoter regions of differentially expressed genes, MYC and Period 1 (PER1), however, did not show any differences in the degree of DNA methylation between controls and clones. Together, these findings demonstrate that cloned pigs have altered gene expression that may potentially cause organ dysfunction.

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Section: Park Et Almentioning

confidence: 73%

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Park

Lai²,

Samuel³

et al. 2011

Cellular Reprogramming

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“…Dietary choline deficiency not only depletes choline and choline metabolites in rats, but also decreases S-adenosylmethionine concentrations (117,164), with resulting hypomethylation of DNA (74,134). DNA methylation occurs at cytosine bases that are followed by a guanosine (CpG sites) (52) and influences many cellular events, including gene transcription, genomic imprinting, and genomic stability (60,64,105).…”

Section: Choline and Brain Development In Uteromentioning

confidence: 99%

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

2006

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Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.

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“…During choline deficiency, hepatic SAM concentrations are decreased by as much as 50% [45][46][47][48]. Animals fed diets deficient in methyl donors (choline and methionine) have hypomethylated DNA [49][50][51]. These deficiencies have been shown to cause both global [52] and gene-specific hypomethylation [53].…”

Section: Animal Studiesmentioning

confidence: 99%

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Duric

Sivanesan

Bakovic

2012

Euro J Lipid Sci & Tech

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Non‐alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin‐based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole‐body metabolic pathologies in many areas of the world.

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Hypomethylation of CpG Sites and c‐myc Gene Overexpression in Hepatocellular Carcinomas, but Not Hyperplastic Nodules, Induced by a Choline‐deficient L‐Amino Acid‐defined Diet in Rats

Cited by 91 publications

References 21 publications

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

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