Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells.
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.
The First Affiliated Hospital, Fujian Medical University, Fuzhou, PR China.
Peng
P
Chen
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China.
Jian-Feng
JF
Yao
The Second Affiliated Hospital, Fujian Medical University, Quanzhou, PR China.
Rong-Fu
RF
Huang
Quanzhou Medical College, Quanzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Fang-Fang
FF
Zheng
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Xiao-Hong
XH
Jiang
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Xuan
X
Chen
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Juan
J
Chen
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Ming
M
Li
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Hong-Feng
HF
Huang
Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China.
Yi-Ping
YP
Jiang
The First Affiliated Hospital, Fujian Medical University, Fuzhou, PR China hyffjlyxl@163.com yangxiaoyu683@163.com.
Yan-Fang
YF
Huang
College of Preclinical Medicine, Fujian Medical University, Fuzhou, PR China Institutes of Reproductive Sciences, Fujian Medical University, Fuzhou, PR China The Affiliated Fuzhou First Hospital, Fujian Medical University, Fuzhou, PR China Fuzhou Maternity & Child Healthcare Hospital, Fuzhou, PR China hyffjlyxl@163.com yangxiaoyu683@163.com.
Xiao-Yu
XY
Yang
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051379:Mice; D011799:Quinazolines / Q000494:pharmacology*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*
D001381:Azepines; C518299:BIX 01294; D006657:Histones; D011799:Quinazolines; D017411:Ribonucleoproteins, Small Nuclear; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase
DNA methylation; Snrpn; cellular toxicity; diazepin-quinazolin-amine derivative (BIX-01294); histone dimethylation; mouse embryonic fibroblasts