Nuclear Signalling Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Nucleic Acids Res. 2012 Aug;40(15):7247-56. doi: 10.1093/nar/gks367. Epub 2012 May 16.
Dynamic acetylation of all lysine-4-trimethylated histone H3 is a complex phenomenon involved in Immediate-early gene induction in metazoan eukaryotes. Higher eukaryotes express repeated copies of three closely related H3 variants, inaccessible to genetic analysis. We demonstrate conservation of these phenomena in Dictyostelium which has three single-copy H3 variant genes. Although dynamic acetylation is targeted to two H3 variants which are K4-trimethylated, K9-acetylation is preferentially targeted to one. In cells lacking Set1 methyltransferase and any detectable K4-trimethylation, dynamic acetylation is lost demonstrating a direct link between the two. Gene replacement to express mutated H3 variants reveals a novel interaction between K4-trimethylation on different variants. Cells expressing only one variant show defects in growth, and in induction of a UV-inducible gene, demonstrating the functional importance of variant expression. These studies confirm that dynamic acetylation targeted to H3K4me3 arose early in evolution and reveal a very high level of specificity of histone variant utilization in a simple multicellular eukaryote.
组蛋白 H3 赖氨酸 4 位三甲基化的动态乙酰化是真核生物瞬时早期基因诱导过程中的一个复杂现象。高等真核生物表达三种密切相关的 H3 变体的重复拷贝，这些变体无法进行基因分析。我们在具有三个单拷贝 H3 变体基因的粘菌中证明了这些现象的保守性。尽管动态乙酰化靶向于两种 K4 三甲基化的 H3 变体，但 K9 乙酰化更倾向于靶向于一种。在缺乏 Set1 甲基转移酶和任何可检测到的 K4 三甲基化的细胞中，动态乙酰化消失，表明这两者之间存在直接联系。用表达突变 H3 变体的基因替换表明，不同变体上的 K4 三甲基化之间存在新的相互作用。只表达一种变体的细胞表现出生长缺陷和 UV 诱导基因的诱导缺陷，这表明变体表达的功能重要性。这些研究证实了靶向 H3K4me3 的动态乙酰化在进化早期就出现了，并揭示了在简单的多细胞真核生物中组蛋白变体利用的高度特异性。
