Institute of Molecular and Cellular Biology, Novosibirsk 630090, Russia.
Laboratory of Epigenetics, Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.
J Cell Sci. 2021 Jan 22;134(2):jcs253096. doi: 10.1242/jcs.253096.
We explored functional roles of two H3K9-specific histone methyltransferases of , SetDB1 (also known as Eggless) and Su(var)3-9. Using the DamID approach, we generated the binding profile for SetDB1 in 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.
我们探索了 SETDB1（也称为 Eggless）和 Su(var)3-9 这两种 H3K9 特异性组蛋白甲基转移酶的功能角色。使用 DamID 方法，我们在唾腺染色体上生成了 SETDB1 的结合图谱，并将其与 Su(var)3-9 的图谱进行匹配。与 Su(var)3-9 不同，SETDB1 原来是一种常染色质蛋白，不存在于重复 DNA 区室中，主要局限于广泛表达基因的转录起始位点 (TSS) 和 5'非翻译区 (5'UTR)。SETDB1 还在绝缘子蛋白 CP190 的结合位点上表现出显著的关联。SETDB1 和 H3K9 二甲基化 (me2) 和三甲基化 (me3) 富集位点的重叠程度较低。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区域之外，并且大约一半的 H3K27me3 区域的边界由 SETDB1 与活跃转录的基因一起修饰。根据 SETDB1 分布与 H3K9 甲基化标记之间的相关性较差，我们推测在体细胞中，SETDB1 可能有助于甲基化一组比 H3K9 更广泛的染色体蛋白。此外，SETDB1 可以预期在建立染色质功能域方面发挥作用。
