Department of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
PLoS Genet. 2011 Mar;7(3):e1001354. doi: 10.1371/journal.pgen.1001354. Epub 2011 Mar 31.
Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to being methylated, H3K4 is also acetylated in budding yeast. Genetic studies reveal that the histone acetyltransferases (HATs) Gcn5 and Rtt109 contribute to H3K4 acetylation in vivo. Whilst removal of H3K4ac from euchromatin mainly requires the histone deacetylase (HDAC) Hst1, Sir2 is needed for H3K4 deacetylation in heterochomatin. Using genome-wide chromatin immunoprecipitation (ChIP), we show that H3K4ac is enriched at promoters of actively transcribed genes and located just upstream of H3K4 tri-methylation (H3K4me3), a pattern that has been conserved in human cells. We find that the Set1-containing complex (COMPASS), which promotes H3K4me2 and -me3, also serves to limit the abundance of H3K4ac at gene promoters. In addition, we identify a group of genes that have high levels of H3K4ac in their promoters and are inadequately expressed in H3-K4R, but not in set1Δ mutant strains, suggesting that H3K4ac plays a positive role in transcription. Our results reveal a novel regulatory feature of promoter-proximal chromatin, involving mutually exclusive histone modifications of the same histone residue (H3K4ac and H3K4me).
组蛋白 H3 赖氨酸 4（H3K4）的甲基化是一种进化上保守的修饰，其在基因表达调控中的作用已被广泛研究。相比之下，H3K4 乙酰化（H3K4ac）的功能由于缺乏分离其与 H3K4me 功能的工具而受到较少关注。在这里，我们证明在芽殖酵母中，除了被甲基化之外，H3K4 还被乙酰化。遗传研究表明，组蛋白乙酰转移酶（HATs）Gcn5 和 Rtt109 有助于体内的 H3K4 乙酰化。虽然常染色质中 H3K4ac 的去除主要需要组蛋白去乙酰化酶（HDAC）Hst1，但异染色质中 H3K4 的去乙酰化需要 Sir2。通过全基因组染色质免疫沉淀（ChIP），我们发现 H3K4ac 在转录活跃的基因启动子处富集，并且位于 H3K4 三甲基化（H3K4me3）的上游，这种模式在人类细胞中得到了保守。我们发现，促进 H3K4me2 和 -me3 的 Set1 包含复合物（COMPASS）也有助于限制基因启动子处 H3K4ac 的丰度。此外，我们鉴定了一组基因，其启动子中具有高水平的 H3K4ac，并且在 H3-K4R 中表达不足，但在 set1Δ 突变株中没有，这表明 H3K4ac 在转录中发挥积极作用。我们的结果揭示了一种涉及同一组蛋白残基（H3K4ac 和 H3K4me）的互斥组蛋白修饰的新型启动子近端染色质调节特征。
