School of Life Sciences, Jilin University, Changchun, People's Republic of China.
PTM BioLabs, Inc, Hangzhou, People's Republic of China.
Biomed Pharmacother. 2017 Aug;92:896-904. doi: 10.1016/j.biopha.2017.05.106. Epub 2017 Jun 7.
Histone lysine methylation, which plays an important role in the regulation of gene expression, genome stability, chromosome conformation and cell differentiation, is a dynamic process that is collaboratively regulated by lysine methyltransferases (KMTs) and lysine demethylases (KDMs). LSD1, the first identified KDMs, catalyzes the demethylation of mono- and di-methylated H3K4 and H3K9. Here, we systematically investigated the effects of LSD1 knockdown on histone methylations. Surprisingly, in addition to H3K4 and H3K9, the methylation level on other histone lysines, such as H3K27, H3K36 and H3K79, are also increased. The expression of SOX2, E-cadherin and FoxA2 are increased upon LSD1 knockdown, and the methylation level of H3K4, H3K27 and H3K36 in the promoter region of these genes are all changed after LSD1 knockdown. Our results show that LSD1 knockdown has a broad effect on histone lysine methylation, which indicates that LSD1 regulates histone lysine methylation in collaboration with other KMTs and KDMs.
组蛋白赖氨酸甲基化在基因表达调控、基因组稳定性、染色体构象和细胞分化中起着重要作用，是一个由赖氨酸甲基转移酶（KMTs）和赖氨酸去甲基化酶（KDMs）共同调控的动态过程。LSD1 是第一个被鉴定的 KDMs，它催化单甲基化和二甲基化 H3K4 和 H3K9 的去甲基化。在这里，我们系统地研究了 LSD1 敲低对组蛋白甲基化的影响。令人惊讶的是，除了 H3K4 和 H3K9 之外，其他组蛋白赖氨酸（如 H3K27、H3K36 和 H3K79）的甲基化水平也增加了。LSD1 敲低后，SOX2、E-钙黏蛋白和 FoxA2 的表达增加，这些基因启动子区域的 H3K4、H3K27 和 H3K36 的甲基化水平在 LSD1 敲低后都发生了变化。我们的结果表明，LSD1 敲低对组蛋白赖氨酸甲基化有广泛的影响，这表明 LSD1 与其他 KMTs 和 KDMs 共同调节组蛋白赖氨酸甲基化。
