Gene transcription is intimately linked to chromatin state and histone modifications. However, the enzymes mediating these post-translational modifications have many additional, nonhistone substrates, making it difficult to ascribe the most relevant modification. In this issue of Genes & Development, Crain and colleagues (doi:10.1101/gad.351698.124) have combined a powerful histone replacement system with mutational analysis of a chromatin regulator and a chromatin reader in Drosophila melanogaster. Importantly, they discovered that genes controlled by the histone 4 lysine 20 (H4K20) methyltransferase Set8 and the protein recognizing H4K20 monomethylation, L(3)mbt, differ substantially from those affected by mutation of H4K20 itself. This demonstrates that H4K20 is not the key substrate for Set8 but that methylation of other, unidentified proteins mediates its effects on transcription.

中文翻译：

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组蛋白之外：染色质调节因子难以捉摸的底物


基因转录与染色质状态和组蛋白修饰密切相关。然而，介导这些翻译后修饰的酶具有许多额外的非组蛋白底物，因此很难归因于最相关的修饰。在本期《基因与发育》中，Crain 及其同事 (doi:10.1101/gad.351698.124) 将强大的组蛋白替代系统与果蝇染色质调节因子和染色质读取器的突变分析相结合。重要的是，他们发现由组蛋白 4 赖氨酸 20 (H4K20) 甲基转移酶 Set8 和识别 H4K20 单甲基化的蛋白质 L(3)mbt 控制的基因与受 H4K20 本身突变影响的基因有很大不同。这表明 H4K20 不是 Set8 的关键底物，而是其他未识别蛋白质的甲基化介导了其对转录的影响。