Change of epigenetic control of cystathionine beta-synthase gene expression through dietary vitamin B12 is not recovered by methionine supplementation.
OBJECTIVE
Vitamin B12 (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial.


METHODS
We raised severely B-12-deficient rats as well severely-B-12 deficient rats but supplemented with 5% methionine. mRNA levels of methionine cycle-related enzymes were analyzed.


RESULTS
Gene expression patterns changed under B-12-deficient conditions but were recovered by dietary methionine supplementation to B-12-deficient rats. However, cystathionine beta-synthase mRNA levels, which had decreased under B-12-deficient conditions, did not recover with supplementary dietary methionine. The CpG island of the cystathionine beta-synthase promoter was hypomethylated in B-12-deficient rats, and showed no recovery after methionine addition.


CONCLUSIONS
Dietary B-12 can affect epigenetic machinery by regulating DNA methylation status and dietary methionine may have small effects on DNA methylation.
Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Atsushi
A
Uekawa
Keishuke
K
Katsushima
Asumi
A
Ogata
Tetsunori
T
Kawata
Nozomi
N
Maeda
Ken-Ichi
K
Kobayashi
Akio
A
Maekawa
Tadahiro
T
Tadokoro
Yuji
Y
Yamamoto
D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology; D004032:Diet; D019587:Dietary Supplements; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014805:Vitamin B 12 / Q000494:pharmacology*; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D008715:Methionine; D003541:Cystathionine beta-Synthase; D014805:Vitamin B 12