The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C-elegans
The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C-elegans
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DOI：
10.1016/j.cub.2004.08.062
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发表时间：
2004-09-21
期刊：
影响因子：
9.2
通讯作者：
Strome, S
中科院分区：
文献类型：
--
作者：
Bender, LB;Cao, R;Strome, S
线虫蛋白 MES-2 和 MES-6 是 Polycomb 组 (PcG) 染色质阻遏蛋白 E(Z) 和 ESC 的直系同源物 [1, 2]，与其新伙伴 MES-3 存在于复合物中 [3]。 MES 系统参与雌雄同体种系中 X 染色体的沉默 [4, 5]。母体 MES 功能的丧失会导致种系变性和不育 [6]。我们在这里报告，MES 复合物负责成体种系和早期胚胎中组蛋白 H3 Lys27 (H3-K27) 的二甲基化和三甲基化，并且 MES 依赖性 H3-K27 标记集中在 X 上。另一种 H3-K27 HMT 在成年体细胞卵母细胞和胚胎 PGC 中发挥作用。在 PGC 中，ME；复合物可以特异性地将二甲基H3-K27转化为三甲基H3-K27。 MES 复合物的 HMT 活性似乎依赖于 MES-2 的 SET 结构域。因此，MES-2 将其直系同源物果蝇 E(Z) 和人类 EZH2 加入到已知具有 HMT 功能的 SET 结构域蛋白中（[7] 中已综述）。组蛋白的甲基化对于染色质的长期表观遗传调控非常重要，并且在 X 失活和肿瘤发生等多种过程中发挥着关键作用 [8]。我们的结果有助于理解跨物种 E(Z)/MES-2 复合物的组成和作用。
The C. elegans proteins MES-2 and MES-6, orthologs of the Polycomb group (PcG) chromatin repressors E(Z) and ESC [1, 2], exist in a complex with their novel partner MES-3 [3]. The MES system participates in silencing the X chromosomes in the hermaphrodite germline [4, 5]. Loss of maternal MES function leads to germline degeneration and sterility [6]. We report here that the MES complex is responsible for di- and trimethylation of histone H3 Lys27 (H3-K27) in the adult germline and in early embryos and that MES-dependent H3-K27 marks are concentrated on the X's. Another H3-K27 HMT functions in adult somatic cells oocytes, and the PGCs of embryos. In PGCs, the ME; complex may specifically convert dimethyl to trimethyl H3-K27. The HMT activity of the MES complex appears to be dependent on the SET domain of MES-2. MES-2 thus joins its orthologs Drosophila E(Z) and human EZH2 among SET domain proteins known to function as HMTs (reviewed in [7]). Methylation of histones is important for long-term epigenetic regulation of chromatin and plays a key role in diverse processes such as X inactivation and oncogenesis [8]. Our results contribute to understanding the composition and roles of E(Z)/MES-2 complexes across species.