PMID- 12163711
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20180507
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 132
IP  - 8 Suppl
DP  - 2002 Aug
TI  - DNA methylation in Folbp1 knockout mice supplemented with folic acid during 
      gestation.
PG  - 2457S-2461S
LID - 10.1093/jn/132.8.2457S [doi]
AB  - Periconceptional folic acid supplementation has been shown to prevent up to 70% 
      of neural tube and other birth defects in humans; however, the mechanism is still 
      unknown. In this study, we tested whether defective intracellular folate 
      transport, as achieved by inactivation of the murine folate-binding protein 1 
      (Folbp1), affects global DNA methylation in the liver and brain from gestational 
      day (GD) 15 embryos. Complete Folbp1 inactivation is embryolethal but can be 
      reversed by maternal folinic acid (FA) supplementation, and thus we also tested 
      the effect of FA supplementation on DNA methylation in Folbp1 fetuses. Overall, 
      the extent of global DNA methylation seems to be similar across all genotypes in 
      unsupplemented control Folbp1 mice; however, explicit conclusions regarding 
      Folbp1(-/-) fetuses were not possible because only a single living unsupplemented 
      fetus was viable at GD 15. FA supplementation induced global DNA hypomethylation 
      across all genotypes. FA-induced hypomethylation is most likely due to its 
      ability to inhibit the enzyme glycine hydroxymethyltransferase, thereby 
      inhibiting the homocysteine remethylation cycle necessary to regenerate 
      S-adenosylmethionine, the methyl donor for DNA methyltransferases. Our hypothesis 
      was that due to defective folate transport in Folbp1(-/-) embryos and fetuses, 
      DNA would be hypomethylated, thereby altering the temporal expression of critical 
      genes necessary for normal embryonic development. However, these results suggest 
      that an extended examination of changes in DNA methylation prior to GD 15 is 
      required to unequivocally prove or disprove the hypothesis.
FAU - Finnell, Richard H
AU  - Finnell RH
AD  - Center for Environmental and Genetic Medicine, Institute of Biosciences and 
      Technology, Texas A&M University System Health Science Center, Houston 77030, 
      USA. rfinnell@ibt.tamu.edu
FAU - Spiegelstein, Ofer
AU  - Spiegelstein O
FAU - Wlodarczyk, Bogdan
AU  - Wlodarczyk B
FAU - Triplett, Aleata
AU  - Triplett A
FAU - Pogribny, Igor P
AU  - Pogribny IP
FAU - Melnyk, Stepan
AU  - Melnyk S
FAU - James, Jill S
AU  - James JS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Carrier Proteins)
RN  - 0 (Folate Receptors, GPI-Anchored)
RN  - 0 (Receptors, Cell Surface)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/genetics/*physiology
MH  - *DNA Methylation
MH  - Female
MH  - Folate Receptors, GPI-Anchored
MH  - Folic Acid/*administration & dosage
MH  - Mice
MH  - Mice, Knockout
MH  - Pregnancy
MH  - *Receptors, Cell Surface
EDAT- 2002/08/07 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/08/07 10:00
PHST- 2002/08/07 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/08/07 10:00 [entrez]
AID - 10.1093/jn/132.8.2457S [doi]
PST - ppublish
SO  - J Nutr. 2002 Aug;132(8 Suppl):2457S-2461S. doi: 10.1093/jn/132.8.2457S.