Isoflavones stimulate estrogen receptor-mediated core histone acetylation.
The isoflavones genistein and daidzein and the daidzein metabolite equol have been reported to interact with estrogen receptors (ERs). Some studies indicate that they behave clinically like estrogen in some estrogen-deficiency diseases. However, the detailed molecular mechanism used by these compounds to create beneficial effects in patients with estrogen-related diseases has not been clarified. Using histone acetyltransferase (HAT) assay, we found that equol, genistein, and AglyMax had significant effects on ERalpha-mediated histone acetylation. Although 17beta-estradiol (E2)-dependent HAT activity of steroid receptor coactivators 2 (SRC2) and p300 mediated by ERbeta could be detected, it was weaker than that mediated by ERalpha. Equol, genistein, AglyMax, and daidzein all markedly stimulated ERbeta-mediated histone acetylation. On the other hand, anti-estrogenic compounds ICI 182,780 (ICI) and tamoxifen (TA) did not have an effect on HAT activity mediated by either ERalpha or ERbeta. Our data indicate that estrogenic ligands exert their effects by elevating histone acetylation and coactivator activity of ER, and suggest that the risk of estrogen-related diseases might be reduced by a sufficient amount of genistein or AglyMax supplements.
Hong
Tao
T
Department of Biochemistry, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Nakagawa
Takeya
T
Pan
WeiJun
W
Kim
Mi Young
MY
Kraus
W Lee
WL
Ikehara
Tsuyoshi
T
Yasui
Kiyoshi
K
Aihara
Hitoshi
H
Takebe
Minoru
M
Muramatsu
Masami
M
Ito
Takashi
T
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000737:chemistry; D060754:Equol; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology; D013629:Tamoxifen / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D004965:Estrogen Antagonists; D006657:Histones; D007529:Isoflavones; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D060754:Equol; C004742:daidzein; D019833:Genistein; D000123:Acetyltransferases; D051548:Histone Acetyltransferases