Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells

被引：15

作者：

Chen, Peng ^{[1
]}

Yao, Jian-Feng ^{[2
]}

Huang, Rong-Fu ^{[3
]}

Zheng, Fang-Fang ^{[4
,5
]}

Jiang, Xiao-Hong ^{[2
,5
]}

Chen, Xuan ^{[2
,5
]}

Chen, Juan ^{[2
,5
]}

Li, Ming ^{[2
,5
]}

Huang, Hong-Feng ^{[2
,5
]}

Jiang, Yi-Ping ^{[5
]}

Huang, Yan-Fang ^{[1
]}

Yang, Xiao-Yu ^{[2
,5
,6
,7
]}

机构：

[1] Fujian Med Univ, Affiliated Hosp 1, Fuzhou, Peoples R China

[2] Fujian Med Univ, Coll Preclin Med, Fuzhou, Peoples R China

[3] Fujian Med Univ, Affiliated Hosp 2, Quanzhou, Peoples R China

[4] Quanzhou Med Coll, Quanzhou, Peoples R China

[5] Fujian Med Univ, Inst Reprod Sci, Fuzhou, Peoples R China

[6] Fujian Med Univ, Affiliated Fuzhou Hosp 1, Fuzhou, Peoples R China

[7] Fuzhou Matern & Child Healthcare Hosp, Fuzhou, Peoples R China

来源：

BIOSCIENCE REPORTS | 2015年 / 35卷

基金：

中国国家自然科学基金;

关键词：

diazepin-quinazolin-amine derivative (BIX-01294); cellular toxicity; DNA methylation; histone dimethylation; mouse embryonic fibroblasts; Snrpn; PLURIPOTENT STEM-CELLS; HISTONE METHYLTRANSFERASE; DNA METHYLATION; EPIGENETIC MODIFICATIONS; NUCLEAR TRANSFER; CPG METHYLATION; G9A; PROLIFERATION; ABNORMALITIES; DIMETHYLATION;

D O I：

10.1042/BSR20150064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Histone H3 lysine 9 dimethylation (H3K9me2) hypermethylation is thought to be a major influential factor in cellular reprogramming, such as somatic cell nuclear transfer (SCNT) and induction of pluripotent stem cells (iPSCs). The diazepin-quinazolin-amine derivative (BIX-01294) specifically inhibits the activity of histone methyltransferase EHMT2 (euchromatic histone-lysine N-methyltransferase 2) and reduces H3K9me2 levels in cells. The imprinted gene small nuclear ribonucleoprotein N (Snrpn) is of particular interest because of its important biological functions. The objective of the present study was to investigate the effect of BIX-01294 on H3K9me2 levels and changes in Snrpn DNA methylation and histone H3K9me2 in mouse embryonic fibroblasts (MEFs). Results showed that 1.3 mu M BIX-01294 markedly reduced global levels of H3K9me2 with almost no cellular toxicity. There was a significant decrease in H3K9me2 in promoter regions of the Snrpn gene after BIX-01294 treatment. A significant increase in methylation of the Snrpn differentially methylated region 1 (DMR1) and slightly decreased transcript levels of Snrpn were found in BIX-01294-treated MEFs. These results suggest that BIX-01294 may reduce global levels of H3K9me2 and affect epigenetic modifications of Snrpn in MEFs.

引用

页数：9

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