期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 426, 期 20, 页码 3426-3441出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2014.07.025
关键词
EZH2; gene expression; estrogen signaling; endocrine disruptors; epigenetics
资金
- National Institutes of Health [1R15 ES019129-01, 2R15CA113747-02]
- National Science Foundation [0821969]
- American Heart Association [0765160Y]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0821969] Funding Source: National Science Foundation
Enhancer of Zeste homolog 2 (EZH2), a methyltransferase specific to histone 3 lysine 27, is a critical player in gene silencing and is overexpressed in breast cancer. Our studies demonstrate that EZH2 is transcriptionally induced by estradiol in cultured breast cancer cells and in the mammary glands of ovariectomized rats. EZH2 promoter contains multiple functional estrogen-response elements. Estrogen receptors (ERs) and ER coregulators such as mixed lineage leukemia (MLL) histone methylases (MLL2 and MLL3) and histone acetyltransferase CBP/P300 bind to the EZH2 promoter in the presence of estradiol and regulate estradiol-induced EZH2 expression. EZH2 expression is also increased upon exposure to estrogenic endocrine disrupting chemicals (EDCs) such as bisphenol-A (BPA) and diethylstilbestrol (DES). Similar to estradiol, BPA and DES-induced EZH2 expression is coordinated by ERs, MLLs and CBP/P300. In summary, we demonstrate that EZH2 is transcriptionally regulated by estradiol in vitro and in vivo, and its expression is potentially dysregulated upon exposure to estrogenic EDCs. (C) 2014 Published by Elsevier Ltd.
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