Department of Urology, University of Southern California, Los Angeles, California, USA.
Mol Cell Biol. 2010 Jun;30(12):2933-46. doi: 10.1128/MCB.01478-09. Epub 2010 Apr 19.
Histone lysine methylation and CpG DNA methylation contribute to transcriptional regulation. We have shown previously that dimethylated and trimethylated forms of histone H3 at lysine 4 (H3K4me2 and H3K4me3) are primarily depleted from CpG-methylated DNA regions by using patch-methylated stable episomes (minichromosomes) in human cells. This effect on H3K4me2 is clearly not linked to the transcriptional activity in the methylated DNA region; however, transcriptional activity may play a role in the presence of H3K4me3. Here, we present clear evidence of the impact of transcriptional activity on the overall level of H3K4me3 in the coding region and the lack of impact on H3K4me2. Our data also demonstrate the influence of transcriptional activity on the distribution of H3K4me3 and H3K4me2, but not that of total H3, in the 5' end of the coding region relative to the 3' end. The nature of the promoter (viral or endogenous) affects H3K4me3 much more than it affects H3K4me2, suggesting a potential fundamental difference in the recruitment of methyltransferase for H3K4 trimethylation.
组蛋白赖氨酸甲基化和 CpG 二甲基化有助于转录调控。我们之前已经表明，在人类细胞中，通过使用经补丁甲基化的稳定附加体（微染色体），组蛋白 H3 赖氨酸 4 上的二甲基和三甲基形式（H3K4me2 和 H3K4me3）主要从 CpG 甲基化 DNA 区域中耗尽。这种对 H3K4me2 的影响显然与甲基化 DNA 区域中的转录活性无关；然而，转录活性可能在存在 H3K4me3 时发挥作用。在这里，我们提供了明确的证据表明转录活性对编码区域中 H3K4me3 的整体水平有影响，而对 H3K4me2 没有影响。我们的数据还表明，转录活性对编码区 5'端 H3K4me3 和 H3K4me2 的分布有影响，但对 3'端的总 H3 没有影响。启动子的性质（病毒或内源性）对 H3K4me3 的影响比对 H3K4me2 的影响大得多，这表明用于 H3K4 三甲基化的甲基转移酶的募集可能存在潜在的根本差异。
