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Gender Difference In Response to Dietary Genistein‐induced Chromatin Remodeling of Wnt Genes in Preneoplastic Rat Colon
Author(s) -
Bray Julie K,
Zhang Yukun,
Chen Hong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.772.4
Subject(s) - genistein , wnt signaling pathway , epigenetics , histone , chromatin immunoprecipitation , biology , chromatin , endocrinology , chromatin remodeling , medicine , colorectal cancer , acetylation , cancer research , dna methylation , gene expression , gene , signal transduction , cancer , microbiology and biotechnology , genetics , promoter
Genistein, a soy‐derived isoflavone, has been reported to reduce the abnormal Wnt signaling that is observed in most colon cancer through epigenetic regulations. In this study, we investigated the effects of dietary genistein on gene expression of the Wnt pathway by histone modifications in the descending colon of rats. Using the azoxymethane‐induced rat colon cancer model, we have identified that dietary genistein reduced the formation of preneoplastic lesions in the colon of female rats more significantly compared to males. Expression of Wnt1 , Wnt6 , and Wnt8b was upregulated, while c‐Myc was downregulated by dietary genistein in female but not in male. By chromatin immunoprecipitation assay, we identified gender‐related differences in dietary genistein‐induced chromatin remodeling, which includes histone acetylation, methylation and phosphorylation at the above‐mentioned Wnt signaling gene regions. The differences were correlated with the differential response in gene expression to genistein between genders. In conclusion, our results suggest an epigenetic mechanism by which dietary genistein differentially affects the Wnt genes and Wnt signaling in male and female during colon cancer development. This study may facilitate establishment of a gender‐based recommendation on dietary genistein intake in maintaining colon health. Grant support : Illinois Soybean Association and NIH/NCI