Monomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8^null, H4^K20R/A, and l(3)mbt mutant Drosophila melanogaster. We found that the gene expression profiles of H4^K20A and H4^K20R larvae are markedly different than Set8^null larvae despite similar reductions in H4K20me1. Set8^null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4^K20, indicating that the developmental defects of Set8^null animals are largely due to H4K20me1-independent effects on gene expression. Furthermore, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8^null and H4^K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin and therefore that H4K20me1 does not play a large role in gene expression.

中文翻译：

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黑腹果蝇 Set8 和 L（3）mbt 在独立于组蛋白 H4 赖氨酸 20 甲基化的基因表达中发挥作用


组蛋白 H4 赖氨酸 20 （H4K20me1） 的单甲基化由 Set8 催化，并被认为在 H4K20me 结合蛋白介导的基因组功能的许多方面发挥重要作用。我们通过平行比较 Set8^null、H4^K20R/A 和 l（3）mbt 突变型黑腹果蝇的转录组，在发育中的动物中询问了该模型。我们发现 H4^K20A 和 H4^K20R 幼虫的基因表达谱与 Set8^无效幼虫明显不同，尽管 H4K20me1 也有类似的减少。Set8^缺失突变细胞的转录组严重被破坏，无法在体内增殖，但这些表型并未被 H4^K20 突变概括，表明 Set8^缺失动物的发育缺陷主要是由于 H4K20me1 对基因表达的非依赖性影响。此外，H4K20me1 结合蛋白 L（3）mbt 被募集到大多数基因的转录起始位点，独立于 H4K20me，即使与 L（3）mbt 结合的基因具有高水平的 H4K20me1。此外，Set8 和 L（3）mbt 在体外都与纯化的 H4K20R 核小体结合。我们得出结论，Set8^无效和 H4^K20 突变体的基因表达变化不能用 H4K20me1 或 L（3）mbt 与染色质结合的缺失来解释，因此 H4K20me1 在基因表达中起不大作用。