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

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.

SUBMITTER: Chen P

PROVIDER: S-EPMC4613706 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We characterized expression profilings of SMYD2 knockdown and control cells treated by BIX-01294 and Rapamycin.

2015-01-01 | GSE61255 | GEO

SMYD2 specificly regulate BIX-01294 induced TP53 target genes revealed by RNA-Seq

Project description:We characterized expression profilings of SMYD2 knockdown and control cells treated by BIX-01294 and Rapamycin. We used siRNAs to knockdown SMYD2 in HCT116 cells, and NC as control. We treated those cell lines with BIX-01294 and Rapamycin, and the expression profilings were perfomed by Illumina high throughput sequencing.

2015-01-01 | E-GEOD-61255 | biostudies-arrayexpress

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