We explored functional roles of two H3K9-specific histone methyltransferases of Drosophila melanogaster, SetDB1 (also known as Eggless) and Su(var)3-9. Using the DamID approach, we generated the binding profile for SetDB1 in Drosophila salivary gland chromosomes, and matched it to the profile of Su(var)3-9. Unlike Su(var)3-9, SetDB1 turned out to be an euchromatic protein that is absent from repeated DNA compartments, and is largely restricted to transcription start sites (TSSs) and 5' untranslated regions (5'UTRs) of ubiquitously expressed genes. Significant SetDB1 association is also observed at binding sites for the insulator protein CP190. SetDB1 and H3K9 di- and tri-methylated (me2 and me3)-enriched sites tend to display poor overlap. At the same time, SetDB1 has a clear connection with the distribution of H3K27me3 mark. SetDB1 binds outside the domains possessing this modification, and about half of the borders of H3K27me3 domains are decorated by SetDB1 together with actively transcribed genes. On the basis of poor correlation between the distribution of SetDB1 and H3K9 methylation marks, we speculate that, in somatic cells, SetDB1 may contribute to the methylation of a broader set of chromosomal proteins than just H3K9. In addition, SetDB1 can be expected to play a role in the establishment of chromatin functional domains.

我们探讨了黑腹果蝇、SetDB1（也称为 Eggless）和 Su(var)3-9的两种 H3K9 特异性组蛋白甲基转移酶的功能作用。使用 DamID 方法，我们为果蝇中的 SetDB1 生成了绑定配置文件唾液腺染色体，并将其与 Su(var)3-9 的轮廓相匹配。与 Su(var)3-9 不同，SetDB1 原来是一种常染色质蛋白，在重复的 DNA 区室中不存在，并且主要局限于普遍表达基因的转录起始位点 (TSS) 和 5' 非翻译区 (5'UTR) . 在绝缘体蛋白 CP190 的结合位点也观察到了显着的 SetDB1 关联。SetDB1 和 H3K9 二甲基化和三甲基化（me2 和 me3）富集的位点往往显示较差的重叠。同时，SetDB1 与 H3K27me3 标记的分布有明显的联系。SetDB1 结合在具有这种修饰的结构域之外，H3K27me3 结构域的大约一半边界被 SetDB1 与活跃转录的基因一起修饰。基于 SetDB1 和 H3K9 甲基化标记的分布之间的相关性较差，我们推测，在体细胞中，SetDB1 可能有助于更广泛的染色体蛋白的甲基化，而不仅仅是 H3K9。此外，SetDB1 有望在染色质功能域的建立中发挥作用。