Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University-School of Osteopathic Medicine, Stratford, NJ 08084, USA.
Biochemistry and Molecular Biology Program, School of Natural Sciences and Mathematics, Stockton University, Galloway, NJ 08205, USA.
G3 (Bethesda). 2021 Oct 19;11(11). doi: 10.1093/g3journal/jkab283.
Meiosis-specific chromatin structures, guided by histone modifications, are critical mediators of a meiotic transient transcription program and progression through prophase I. Histone H3K4 can be methylated up to three times by the Set1-containing COMPASS complex and each methylation mark corresponds to a different chromatin conformation. The level of H3K4 modification is directed by the activity of additional COMPASS components. In this study, we characterized the role of the COMPASS subunits during meiosis in Saccharomyces cerevisiae. In vegetative cells, previous studies revealed a role for subunits Swd2, Sdc1, and Bre2 for H3K4me2 while Spp1 supported trimethylation. However, we found that Bre2 and Sdc1 are required for H3K4me3 as yeast prepare to enter meiosis while Spp1 is not. Interestingly, we identified distinct meiotic functions for the core COMPASS complex members that required for all H3K4me, Set1, Swd1, and Swd3. While Set1 and Swd1 are required for progression through early meiosis, Swd3 is critical for late meiosis and spore morphogenesis. Furthermore, the meiotic requirement for Set1 is independent of H3K4 methylation, suggesting the presence of nonhistone substrates. Finally, checkpoint suppression analyses indicate that Set1 and Swd1 are required for both homologous recombination and chromosome segregation. These data suggest that COMPASS has important new roles for meiosis that are independent of its well-characterized functions during mitotic divisions.
减数分裂特异性染色质结构,由组蛋白修饰指导,是减数分裂瞬时转录程序和通过前期 I 进展的关键介质。组蛋白 H3K4 可以被包含 Set1 的 COMPASS 复合物甲基化多达三次,每个甲基化标记对应于不同的染色质构象。H3K4 修饰的水平由其他 COMPASS 成分的活性指导。在这项研究中,我们研究了 COMPASS 亚基在酿酒酵母减数分裂中的作用。在营养细胞中,先前的研究表明 Swd2、Sdc1 和 Bre2 亚基在 H3K4me2 方面发挥作用,而 Spp1 支持三甲基化。然而,我们发现 Bre2 和 Sdc1 对于酵母准备进入减数分裂时的 H3K4me3 是必需的,而 Spp1 则不是。有趣的是,我们鉴定了核心 COMPASS 复合物成员的独特减数分裂功能,这些成员对于所有 H3K4me、Set1、Swd1 和 Swd3 都是必需的。虽然 Set1 和 Swd1 对于早期减数分裂的进展是必需的,但 Swd3 对于晚期减数分裂和孢子形态发生是至关重要的。此外,Set1 在减数分裂中的需求独立于 H3K4 甲基化,这表明存在非组蛋白底物。最后,检查点抑制分析表明 Set1 和 Swd1 对于同源重组和染色体分离都是必需的。这些数据表明,COMPASS 在减数分裂中具有重要的新作用,这些作用独立于其在有丝分裂分裂中的特征功能。