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学科主题: 临床医学
题名:
Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter
作者: Wu, Li-Peng1,2; Wang, Xi1; Li, Lian1; Zhao, Ying1,2; Lu, Shaoli1; Yu, Yu1; Zhou, Wen1; Liu, Xiangyu1; Yang, Jing1; Zheng, Zhixin1; Zhang, Hui1,3; Feng, Jingnan1; Yang, Yang1; Wang, Haiying1; Zhu, Wei-Guo1,2
刊名: MOLECULAR AND CELLULAR BIOLOGY
发表日期: 2008-05-01
DOI: 10.1128/MCB.01516-07
卷: 28, 期:10, 页:3219-3235
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: TUMOR-SUPPRESSOR GENE ; HUMAN CANCER-CELLS ; DNA CYTOSINE-5 METHYLTRANSFERASES ; DE-NOVO METHYLATION ; MAINTENANCE METHYLATION ; LYSINE-9 METHYLATION ; EARLY EMBRYOGENESIS ; P-GLYCOPROTEIN ; HUMAN LUNG ; EXPRESSION
英文摘要:

Histone deacetylase inhibitor (HDACi) has been shown to demethylate the mammalian genome, which further strengthens the concept that DNA methylation and histone modifications interact in regulation of gene expression. Here, we report that an HDAC inhibitor, depsipeptide, exhibited significant demethylating activity on the promoters of several genes, including p16, SALL3, and GATA4 in human lung cancer cell lines H719 and H23, colon cancer cell line HT-29, and pancreatic cancer cell line PANC1. Although expression of DNA methyltransferase 1 (DNMT1) was not affected by depsipeptide, a decrease in binding of DNMT1 to the promoter of these genes played a dominant role in depsipeptide-induced demethylation and reactivation. Depsipeptide also suppressed expression of histone methyltransferases G9A and SUV39H1, which in turn resulted in a decrease of di- and trimethylated H3K9 around these genes′ promoter. Furthermore, both loading of heterochromatin-associated protein 1 (HP1 alpha and HP1 beta) to methylated H3K9 and binding of DNMT1 to these genes′ promoter were significantly reduced in depsipeptide-treated cells. Similar DNA demethylation was induced by another HDAC inhibitor, apicidin, but not by trichostatin A. Our data describe a novel mechanism of HDACi-mediated DNA demethylation via suppression of histone methyltransferases and reduced recruitment of HP1 and DNMT1 to the genes′ promoter.

语种: 英语
WOS记录号: WOS:000255600800012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65522
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Secondary Affiliated Hosp, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Secondary Affiliated Hosp, Sch Oncol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Secondary Affiliated Hosp, Dept Surg, Beijing 100083, Peoples R China

Recommended Citation:
Wu, Li-Peng,Wang, Xi,Li, Lian,et al. Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter[J]. MOLECULAR AND CELLULAR BIOLOGY,2008,28(10):3219-3235.
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