![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vitamin Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111
3To whom correspondence should be addressed. E-mail: sfriso{at}hnrc.tufts.edu.
Many micronutrients and vitamins are critical for DNA synthesis/repair and maintenance of DNA methylation patterns. Folate has been most extensively investigated in this regard because of its unique function as methyl donor for nucleotide synthesis and biological methylation. Cell culture and animal and human studies showed that deficiency of folate induces disruption of DNA as well as alterations in DNA methylation status. Animal models of methyl deficiency demonstrated an even stronger cause-and-effect relationship than did studies using a folate-deficient diet alone. Such observations imply that the adverse effects of inadequate folate status on DNA metabolism are mostly due to the impairment of methyl supply. Recently, an interaction was observed between folate status and a common mutation in the gene encoding for methylenetetrahydrofolate reductase, an essential enzyme in one-carbon metabolism, in determining genomic DNA methylation. This finding suggests that the interaction between a nutritional status with a genetic polymorphism can modulate gene expression through DNA methylation, especially when such polymorphism limits the methyl supply. DNA methylation, both genome-wide and gene-specific, is of particular interest for the study of cancer, aging and other conditions related to cell-cycle regulation and tissue-specific differentiation, because it affects gene expression without permanent alterations in DNA sequence such as mutations or allele deletions. Understanding the patterns of DNA methylation through the interaction with nutrients is fundamental, not only to provide pathophysiological explanations for the development of certain diseases, but also to improve the knowledge of possible prevention strategies by modifying a nutritional status in at-risk populations.
KEY WORDS: • MTHFR • C677T • folate • DNA methylation • gene expression
This article has been cited by other articles:
|
|
 |
|
  I. Elmadfa and I. Singer Vitamin B-12 and homocysteine status among vegetarians: a global perspective Am. J. Clinical Nutrition, May 1, 2009; 89(5): 1693S - 1698S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Foley, J. M. Craig, R. Morley, C. J. Olsson, T. Dwyer, K. Smith, and R. Saffery Prospects for Epigenetic Epidemiology Am. J. Epidemiol., February 15, 2009; 169(4): 389 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Brown and E. S. Susser Prenatal Nutritional Deficiency and Risk of Adult Schizophrenia Schizophr Bull, November 1, 2008; 34(6): 1054 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D. Smith, Y.-I. Kim, and H. Refsum Is folic acid good for everyone? Am. J. Clinical Nutrition, March 1, 2008; 87(3): 517 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Keyes, H. Jang, J. B. Mason, Z. Liu, J. W. Crott, D. E. Smith, S. Friso, and S.-W. Choi Older Age and Dietary Folate Are Determinants of Genomic and p16-Specific DNA Methylation in Mouse Colon J. Nutr., July 1, 2007; 137(7): 1713 - 1717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Chang, K. M. Balter, A. Torrang, K. E. Smedby, M. Melbye, C. Sundstrom, B. Glimelius, and H.-O. Adami Nutrient Intake and Risk of Non-Hodgkin's Lymphoma Am. J. Epidemiol., December 15, 2006; 164(12): 1222 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Oltean and R. Banerjee A B12-responsive Internal Ribosome Entry Site (IRES) Element in Human Methionine Synthase J. Biol. Chem., September 23, 2005; 280(38): 32662 - 32668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Dorward, K. L. Shultz, L. G. Horton, R. Li, G. A. Churchill, and W. G. Beamer Distal Chr 4 Harbors a Genetic Locus (Gct1) Fundamental for Spontaneous Ovarian Granulosa Cell Tumorigenesis in a Mouse Model Cancer Res., February 15, 2005; 65(4): 1259 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. de Fourmestraux, H. Neubauer, C. Poussin, P. Farmer, L. Falquet, R. Burcelin, M. Delorenzi, and B. Thorens Transcript Profiling Suggests That Differential Metabolic Adaptation of Mice to a High Fat Diet Is Associated with Changes in Liver to Muscle Lipid Fluxes J. Biol. Chem., December 3, 2004; 279(49): 50743 - 50753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lund, L. Andersson, M. Lauria, M. Lindholm, M. F. Fraga, A. Villar-Garea, E. Ballestar, M. Esteller, and S. Zaina DNA Methylation Polymorphisms Precede Any Histological Sign of Atherosclerosis in Mice Lacking Apolipoprotein E J. Biol. Chem., July 9, 2004; 279(28): 29147 - 29154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Fukagawa and R. A. Galbraith Advancing Age and Other Factors Influencing the Balance between Amino Acid Requirements and Toxicity J. Nutr., June 1, 2004; 134(6): 1569S - 1574S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-I. Kim Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer? Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 511 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Choi, S. Friso, H. Ghandour, P. J. Bagley, J. Selhub, and J. B. Mason Vitamin B-12 Deficiency Induces Anomalies of Base Substitution and Methylation in the DNA of Rat Colonic Epithelium J. Nutr., April 1, 2004; 134(4): 750 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Bailey Folate, Methyl-Related Nutrients, Alcohol, and the MTHFR 677C->T Polymorphism Affect Cancer Risk: Intake Recommendations J. Nutr., November 1, 2003; 133(11): 3748S - 3753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. V. Oleinik and S. A. Krupenko Ectopic Expression of 10-Formyltetrahydrofolate Dehydrogenase in A549 Cells Induces G1 Cell Cycle Arrest and Apoptosis Mol. Cancer Res., June 1, 2003; 1(8): 577 - 588. [Abstract] [Full Text] [PDF]
|
|
