Molecular Biology Reports

, Volume 33, Issue 4, pp 253–256 | Cite as

DNA methylation, riboswitches, and transcription factor activity: fundamental mechanisms of gene–nutrient interactions involving vitamins



Nutrient–gene interactions occur with a variety of nutrients including some minerals, vitamins, polyunsaturated fatty acids and other lipids. Fundamental molecular mechanisms that underlie many of the effects of nutrients on gene expression are presented herein. Two of the mechanisms described influence gene transcription: DNA methylation and transcription factor activation. Another mechanism, riboswitching, can regulate gene expression at different levels, for example, at the mRNA translation level. The first two mechanisms are widely distributed across animal phyla. Riboswitches are documented primarily in more primitive organisms, but may prove to be of wider relevance. Riboswitches are known for several vitamins; those involving thiamine are presented here. The role of folates and retinoids in DNA methylation and transcriptional factor (nuclear retinoid receptor) activities, respectively, is presented in the context of cell proliferation and differentiation, and related physiological or pathological effects during embryogenesis and cancer.


DNA methylation Gene–nutrient interactions Folate Retinoids Riboswitches Thiamine Transcription Vitamins 


  1. 1.
    Wiens M, Batel R, Korzhev M, Muller WE (2003) Retinoid X receptor and retinoic acid response in Suberites domuncula. J Exp Biol 206:3261–3271PubMedCrossRefGoogle Scholar
  2. 2.
    Vieira AV (1998) Retinoid endocrinology from metabolism to cellular signaling. In: Quinn PJ, Kagan VE (eds) Subcellular biochememistry: fat-soluble vitamins, vol 30. NY, USA, pp 29–51Google Scholar
  3. 3.
    Chambon P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10:940–954PubMedGoogle Scholar
  4. 4.
    Allenby G, Bocquel M, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P, Levin AA (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 90:30–34PubMedCrossRefGoogle Scholar
  5. 5.
    Nagpal S, Friant S, Nakshatri H, Chambon P (1993) RARs and RXRs: evidence for two autonomous transactivation functions and heterodimerization in vivo. EMBO J 12:2349–2360PubMedGoogle Scholar
  6. 6.
    Bastien J, Rochette-Egly C (2004) Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 328:1–16PubMedCrossRefGoogle Scholar
  7. 7.
    Kastner P, Grondona JM, Mark M, Gansmuller A, LeMeur M, Decimo D, Vonesch J-L, Dolle P, Chambon P (1994) Genetic analysis of RXR developmental functions: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell 78:987–1003PubMedCrossRefGoogle Scholar
  8. 8.
    Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P (1993) Function of retinoic acid receptor in the mouse. Cell 73:643–658PubMedCrossRefGoogle Scholar
  9. 9.
    Finnell RH, Shaw GM, Lammer EJ, Brandl KL, Carmichael SL, Rosenquist TH (2004) Gene–nutrient interactions: importance of folates and retinoids during early embryogenesis. Toxicol Appl Pharmacol 198:75–85PubMedCrossRefGoogle Scholar
  10. 10.
    Boylan JF, Lohnes D, Taneja R, Chambon P, Gudas LJ (1993) Loss of RAR function by gene disruption results in aberrant Hoxa-1 expression and defective cell differentiation. Proc Natl Acad Sci USA 90:9601–9605PubMedCrossRefGoogle Scholar
  11. 11.
    Simeone A, Acampora D, Arcioni L, Andrews PW, Boncinelli E, Malvillo F (1990) Sequencial activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346:763–767PubMedCrossRefGoogle Scholar
  12. 12.
    Lotan R (1996) Retinoids in cancer chemoprevention. FASEB J 10:1031–1039PubMedGoogle Scholar
  13. 13.
    Ou X, Campau S, Slusher R, Jasti RK, Mabry M, Kalemkerian GP (1996) Mechanism of all-trans-retinoic acid-mediated L-myc gene regulation in small cell lung cancer. Oncogene 13:1893–1899PubMedGoogle Scholar
  14. 14.
    Houle B, Rochette-Egly C, Bradley WE (1993) Tumor suppressive effect of retinoic acid receptor in human epidermoid lung cancer cells. Proc Natl Acad Sci USA 90:985–989PubMedCrossRefGoogle Scholar
  15. 15.
    Lampert JM, Holzschuh J, Hessel S, Driever W, Vogt K, von Lintig J (2003) Provitamin A conversion to retinal via the beta,beta-carotene-15,15′-oxygenase (bcox) is essential for pattern formation and differentiation during zebrafish embryogenesis. Development 130:2173–2186PubMedCrossRefGoogle Scholar
  16. 16.
    Jordan F (1999) Interplay of organic and biological chemistry in understanding coenzyme mechanisms: example of thiamin diphosphate-dependent decarboxylations of 2-oxo acids. FEBS Lett. 457:298–301PubMedCrossRefGoogle Scholar
  17. 17.
    Winkler W, Nahvi A, Breaker RR (2002) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–956PubMedCrossRefGoogle Scholar
  18. 18.
    Sudarsan N, Barrick JE, Breaker RR (2003) Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9:644–647PubMedCrossRefGoogle Scholar
  19. 19.
    Kaempfer R (2003) RNA sensors: novel regulators of gene expression. EMBO 4:1043–1047CrossRefGoogle Scholar
  20. 20.
    James SJ, Pogribny IP, Pogribna M, Miller BJ, Jernigan S, Melnyk S (2003) Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis. J Nutr 133:3740S–3747SPubMedGoogle Scholar
  21. 21.
    Baylin SB, Makos M, Wu JJ, Yen RW, de Bustros A, Vertino P, Nelkin BD (1991) Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 3:383–390PubMedGoogle Scholar
  22. 22.
    Davis CD, Uthus EO (2004) DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med 229:988–995Google Scholar
  23. 23.
    Rampersaud GC, Kauwell GP, Hutson AD, Cerda JJ, Bailey LB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr. 72:998–1003PubMedGoogle Scholar
  24. 24.
    Shelnutt KP, Kauwell GP, Gregory JF III, Maneval DR, Quinlivan EP, Theriaque DW, Henderson GN, Bailey LB (2004) Methylenetetrahydrofolate reductase 677C–>T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 15:554–560PubMedCrossRefGoogle Scholar
  25. 25.
    Finnell RH, Spiegelstein O, Wlodarczyk B, Triplett A, Pogribny IP, Melnyk S, James JS (2002) DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation. J Nutr 132:2457S–2461SPubMedGoogle Scholar
  26. 26.
    Piedrahita JA, Oetama B, Bennett GD, van Waes J, Kamen BA, Richardson J, Lacey SW, Anderson RG, Finnell RH (1999) Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet 23:228–232PubMedCrossRefGoogle Scholar
  27. 27.
    Shaw GM, Lammer EJ, Wasserman CR, O’Malley CD, Tolarova MM (1995) Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 346:393–396PubMedCrossRefGoogle Scholar
  28. 28.
    Czeizel AE (1993) Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 306:1645–1648PubMedCrossRefGoogle Scholar
  29. 29.
    Nelson MM (1960) Teratogenic effects of pteroylglutamic acid deficiency in the rat. In: Ciba foundation symposium on congenital malformations, John Wiley and Sons, pp 134–157Google Scholar
  30. 30.
    Shiota K, Yanagimachi R (2002) Epigenetics by DNA methylation for development of normal and cloned animals. Differentiation 69:162–166PubMedCrossRefGoogle Scholar
  31. 31.
    Ohgane J, Wakayama T, Kogo Y, Senda S, Hattori N, Tanaka S, Yanagimachi R, Shiota K (2001) DNA methylation variation in cloned mice. Genesis 30:45–50PubMedCrossRefGoogle Scholar
  32. 32.
    Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926PubMedCrossRefGoogle Scholar
  33. 33.
    Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Nutrition and Metabolic Research Laboratory and IHRE, Kin-9625 Applied SciencesSimon Fraser UniversityBurnabyCanada

Personalised recommendations