文章基本信息

标题：Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation
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作者：Xi Zhang ; Kaori Tanaka ; Jiusheng Yan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：43
页码：17284-17289
DOI：10.1073/pnas.1307959110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Estrogen receptor alpha (ER) is a ligand-activated transcription factor. Upon estrogen stimulation, ER recruits a number of coregulators, including both coactivators and corepressors, to the estrogen response elements, modulating gene activation or repression. Most coregulator complexes contain histone-modifying enzymes to control ER target gene expression in an epigenetic manner. In addition to histones, these epigenetic modifiers can modify nonhistone proteins including ER, thereby constituting another layer of transcriptional regulation. Here we show that SET and MYND domain containing 2 (SMYD2), a histone H3K4 and H3K36 methyltransferase, directly methylates ER protein at lysine 266 (K266) both in vitro and in cells. In breast cancer MCF7 cells, SMYD2 attenuates the chromatin recruitment of ER to prevent ER target gene activation under an estrogen-depleted condition. Importantly, the SMYD2-mediated repression of ER target gene expression is mediated by the methylation of ER at K266 in the nucleus, but not the methylation of histone H3K4. Upon estrogen stimulation, ER-K266 methylation is diminished, thereby enabling p300/cAMP response element-binding protein-binding protein to acetylate ER at K266, which is known to promote ER transactivation activity. Our study identifies a previously undescribed inhibitory methylation event on ER. Our data suggest that the dynamic cross-talk between SMYD2-mediated ER protein methylation and p300/cAMP response element-binding protein-binding protein-dependent ER acetylation plays an important role in fine-tuning the functions of ER at chromatin and the estrogen-induced gene expression profiles.
关键词：ERα hinge region ; lysine methylation ; LSD1