Genistein alters methylation patterns in mice.
In this study we examine the effect of the phytoestrogen genistein on DNA methylation. DNA methylation is thought to inhibit transcription of genes by regulating alterations in chromatin structure. Estrogenic compounds have been reported to regulate DNA methylation in a small number of studies. Additionally, phytoestrogens are believed to affect progression of some human diseases, such as estrogen-dependent cancers, osteoporosis and cardiovascular disease. Specifically, our working hypothesis is that certain soy phytoestrogens, such as genistein, may be involved in preventing the development of certain prostate and mammary cancers by maintaining a protective DNA methylation profile. The objective of the present study is to use mouse differential methylation hybridization (DMH) arrays to test for changes in the methylation status of the cytosine guanine dinucleotide (CpG) islands in the mouse genome by examining how these methylation patterns are affected by genistein. Male mice were fed a casein-based diet (control) or the same diet containing 300 mg genistein/kg according to one of four regimens: control diet for 4 wk, genistein diet for 4 wk, control diet for 2 wk followed by genistein diet for 2 wk and genistein diet for 2 wk followed by control diet for 2 wk. DNA from liver, brain and prostate were then screened with DMH arrays. Clones with methylation differences were sequenced and compared with known sequences. In conclusion, consumption of genistein diet was positively correlated with changes in prostate DNA methylation at CpG islands of specific mouse genes.
Day
J Kevin
JK
Department of Biochemistry, University of Missouri, Columbia 65211, USA.
Bauer
Andrew M
AM
DesBordes
Charles
C
Zhuang
Yi
Y
Kim
Byung-Eun
BE
Newton
Leslie G
LG
Nehra
Vedika
V
Forsee
Kara M
KM
MacDonald
Ruth S
RS
Besch-Williford
Cynthia
C
Huang
Tim Hui-Ming
TH
Lubahn
Dennis B
DB
D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D004247:DNA; D019175:DNA Methylation; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization
D004247:DNA; D019833:Genistein