Department of Biochemistry and Molecular Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell. 2012 Aug 31;150(5):922-33. doi: 10.1016/j.cell.2012.06.046. Epub 2012 Aug 23.
Propagation of gene-expression patterns through the cell cycle requires the existence of an epigenetic mark that re-establishes the chromatin architecture of the parental cell in the daughter cells. We devised assays to determine which potential epigenetic marks associate with epigenetic maintenance elements during DNA replication in Drosophila embryos. Histone H3 trimethylated at lysines 4 or 27 is present during transcription but, surprisingly, is replaced by nonmethylated H3 following DNA replication. Methylated H3 is detected on DNA only in nuclei not in S phase. In contrast, the TrxG and PcG proteins Trithorax and Enhancer-of-Zeste, which are H3K4 and H3K27 methylases, and Polycomb continuously associate with their response elements on the newly replicated DNA. We suggest that histone modification enzymes may re-establish the histone code on newly assembled unmethylated histones and thus may act as epigenetic marks.
通过细胞周期传播基因表达模式需要存在一种表观遗传标记,该标记在子细胞中重新建立亲代细胞的染色质结构。我们设计了实验来确定在果蝇胚胎的 DNA 复制过程中哪些潜在的表观遗传标记与表观遗传维持元件相关。在转录过程中存在赖氨酸 4 或 27 处组蛋白 H3 的三甲基化,但令人惊讶的是,在 DNA 复制后,它被未甲基化的 H3 取代。在 S 期以外的核中,仅在 DNA 上检测到甲基化的 H3。相比之下,TrxG 和 PcG 蛋白 Trithorax 和 Enhancer-of-Zeste 是 H3K4 和 H3K27 甲基转移酶,而 Polycomb 则连续与其新复制 DNA 上的反应元件结合。我们认为,组蛋白修饰酶可能在新组装的未甲基化组蛋白上重新建立组蛋白密码,因此可能充当表观遗传标记。