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BIX-01294对小鼠胚胎成纤维细胞中H3K9me2水平及印记基因Snrpn的影响。

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

作者信息

Chen Peng, Yao Jian-Feng, Huang Rong-Fu, Zheng Fang-Fang, Jiang Xiao-Hong, Chen Xuan, Chen Juan, Li Ming, Huang Hong-Feng, Jiang Yi-Ping, Huang Yan-Fang, Yang Xiao-Yu

机构信息

The First Affiliated Hospital, Fujian Medical University, Fuzhou, PR China.

College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China.

出版信息

Biosci Rep. 2015 Aug 18;35(5):e00257. doi: 10.1042/BSR20150064.

DOI:10.1042/BSR20150064
PMID:26285804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4613706/
Abstract

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 μM 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.

摘要

组蛋白H3赖氨酸9二甲基化（H3K9me2）的高甲基化被认为是细胞重编程中的一个主要影响因素，如体细胞核移植（SCNT）和诱导多能干细胞（iPSC）。二氮杂卓-喹唑啉-胺衍生物（BIX-01294）特异性抑制组蛋白甲基转移酶EHMT2（常染色质组蛋白-赖氨酸N-甲基转移酶2）的活性，并降低细胞中的H3K9me2水平。印记基因小核核糖核蛋白N（Snrpn）因其重要的生物学功能而备受关注。本研究的目的是探讨BIX-01294对小鼠胚胎成纤维细胞（MEF）中H3K9me2水平以及Snrpn DNA甲基化和组蛋白H3K9me2变化的影响。结果显示，1.3μM的BIX-01294显著降低了H3K9me2的整体水平，且几乎没有细胞毒性。BIX-01294处理后，Snrpn基因启动子区域的H3K9me2显著降低。在BIX-01294处理的MEF中，发现Snrpn差异甲基化区域1（DMR1）的甲基化显著增加，而Snrpn的转录水平略有下降。这些结果表明，BIX-01294可能会降低MEF中H3K9me2的整体水平，并影响Snrpn的表观遗传修饰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/4f1aa92a008a/bsr035e257fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/19b5c7884ff7/bsr035e257fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/22c8572ec245/bsr035e257fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/c6d2771f054d/bsr035e257fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/c8225df05131/bsr035e257fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/4f1aa92a008a/bsr035e257fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/19b5c7884ff7/bsr035e257fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/22c8572ec245/bsr035e257fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/c6d2771f054d/bsr035e257fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/c8225df05131/bsr035e257fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f9c/4711304/4f1aa92a008a/bsr035e257fig5.jpg

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