N-terminal acetylation of the Set1-COMPASS fine-tunes H3K4 methylation patterns (ChIPseq for ard1 deletion strain)

H3K4 methylation is a conserved histone modification crucial for gene regulation, yet the post-translational modifications of the Set1-COMPASS complex remain largely unexplored. This study elucidates the significance of N-terminal acetylation in modulating H3K4 methylation patterns. Firstly, loss of NatA complex resulted in a significant decrease in H3K4me3 levels and a shift of H3K4me2 from 5' transcribed regions to promoters. Importantly, NatA physically interacted with the Set1-COMPASS complex and facilitated N-terminal acetylation of the Shg1 subunit. Surprisingly, deletion of SHG1 or mutation of the acetylation site (A2P) in Shg1 led to reduced H3K4 methylation in cells lacking Spp1. Additionally, NatB complex also contributed to H3K4 methylation regulation, potentially through N-terminal acetylation of Swd1. These findings highlight the novel role of N-terminal acetylation in fine-tuning the function of the Set1-COMPASS complex and shaping H3K4 methylation patterns. This study sheds light on the intricate regulation of H3K4 methylation and emphasizes the significance of N-terminal acetylation as a regulatory mechanism in this process.H3K4甲基化（H3K4 methylation）是一种高度保守的组蛋白修饰，在基因调控中发挥关键作用，然而目前学界对Set1-COMPASS复合体（Set1-COMPASS complex）的翻译后修饰仍未得到充分探索。本研究阐明了N端乙酰化（N-terminal acetylation）在调控H3K4甲基化模式中的重要意义。 首先，NatA复合体（NatA complex）的缺失会导致H3K4三甲基化（H3K4me3）水平显著下降，并使H3K4二甲基化（H3K4me2）的分布从转录5'区域偏移至启动子区域。 重要的是，NatA可与Set1-COMPASS复合体发生物理互作，并促进Shg1亚基的N端乙酰化修饰。 令人意外的是，在缺失Spp1的细胞中，敲除SHG1基因或突变Shg1的乙酰化位点（A2P）均会导致H3K4甲基化水平降低。 此外，NatB复合体（NatB complex）也参与了H3K4甲基化的调控，其作用机制可能与Swd1的N端乙酰化修饰相关。 本研究揭示了N端乙酰化在精准调控Set1-COMPASS复合体功能、塑造H3K4甲基化模式中的全新作用，阐明了H3K4甲基化的复杂调控机制，并强调了N端乙酰化作为该过程调控机制的重要意义。