Abstract
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.
Similar content being viewed by others
References
Wiens M, Batel R, Korzhev M, Muller WE (2003) Retinoid X receptor and retinoic acid response in Suberites domuncula. J Exp Biol 206:3261–3271
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 29–51
Chambon P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10:940–954
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 90:30–34
Nagpal S, Friant S, Nakshatri H, Chambon P (1993) RARs and RXRs: evidence for two autonomous transactivation functions and heterodimerization in vivo. EMBO J 12:2349–2360
Bastien J, Rochette-Egly C (2004) Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 328:1–16
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 78:987–1003
Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P (1993) Function of retinoic acid receptor in the mouse. Cell 73:643–658
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 198:75–85
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 90:9601–9605
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 346:763–767
Lotan R (1996) Retinoids in cancer chemoprevention. FASEB J 10:1031–1039
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 13:1893–1899
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 90:985–989
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 130:2173–2186
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. 457:298–301
Winkler W, Nahvi A, Breaker RR (2002) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–956
Sudarsan N, Barrick JE, Breaker RR (2003) Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9:644–647
Kaempfer R (2003) RNA sensors: novel regulators of gene expression. EMBO 4:1043–1047
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–3747S
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 3:383–390
Davis CD, Uthus EO (2004) DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med 229:988–995
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. 72:998–1003
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 15:554–560
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–2461S
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 23:228–232
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 346:393–396
Czeizel AE (1993) Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 306:1645–1648
Nelson MM (1960) Teratogenic effects of pteroylglutamic acid deficiency in the rat. In: Ciba foundation symposium on congenital malformations, John Wiley and Sons, pp 134–157
Shiota K, Yanagimachi R (2002) Epigenetics by DNA methylation for development of normal and cloned animals. Differentiation 69:162–166
Ohgane J, Wakayama T, Kogo Y, Senda S, Hattori N, Tanaka S, Yanagimachi R, Shiota K (2001) DNA methylation variation in cloned mice. Genesis 30:45–50
Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257
Acknowledgments
Research in the author’s (AV) laboratory is supported by a grant from Natural Sciences and Engineering Research Council of Canada.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, J., Vieira, A. DNA methylation, riboswitches, and transcription factor activity: fundamental mechanisms of gene–nutrient interactions involving vitamins. Mol Biol Rep 33, 253–256 (2006). https://doi.org/10.1007/s11033-006-9005-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-006-9005-y