Unknown

Dataset Information

0

Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter.


ABSTRACT: 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 (HP1alpha and HP1beta) 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.

SUBMITTER: Wu LP 

PROVIDER: S-EPMC2423178 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter.

Wu Li-Peng LP   Wang Xi X   Li Lian L   Zhao Ying Y   Lu Shaoli S   Yu Yu Y   Zhou Wen W   Liu Xiangyu X   Yang Jing J   Zheng Zhixin Z   Zhang Hui H   Feng Jingnan J   Yang Yang Y   Wang Haiying H   Zhu Wei-Guo WG  

Molecular and cellular biology 20080310 10


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. A  ...[more]

Similar Datasets

| S-EPMC2657887 | biostudies-other
| S-EPMC7019175 | biostudies-literature
| S-EPMC5218499 | biostudies-literature
| S-EPMC105362 | biostudies-literature
| S-EPMC8564726 | biostudies-literature
| S-EPMC7457146 | biostudies-literature
| S-EPMC5497724 | biostudies-literature
| S-EPMC5022900 | biostudies-literature
| S-EPMC7322038 | biostudies-literature
| S-EPMC3023528 | biostudies-literature