Understanding of the appropriate regulation of enzymatic activities of histone-modifying enzymes remains poor. The lysine methyltransferase, SETDB1, is one of the enzymes responsible for the methylation of histone H3 at lysine 9 (H3K9) and plays a key role in H3K9 trimethylation-mediated silencing of genes and retrotransposons. Here, we reported that how SETDB1's enzymatic activities can be regulated by the nuclear protein, ATF7IP, a known binding partner of SETDB1. Mechanistically, ATF7IP mediates SETDB1 retention inside the nucleus, presumably by inhibiting its nuclear export by binding to the N-terminal region of SETDB1, which harbors the nuclear export signal motifs, and also by promoting its nuclear import. The nuclear localization of SETDB1 increases its ubiquitinated, enzymatically more active form. Our results provided an insight as to how ATF7IP can regulate the histone methyltransferase activity of SETDB1 accompanied by its nuclear translocation.

中文翻译：

---

ATF7IP调节SETDB1的核定位并增加其泛素化。

对组蛋白修饰酶的酶活性的适当调节的了解仍然很差。赖氨酸甲基转移酶SETDB1是负责组蛋白H3在赖氨酸9（H3K9）甲基化的酶之一，在H3K9三甲基化介导的基因沉默和转座子沉默中起关键作用。在这里，我们报道了SETDB1的酶促活性如何被核蛋白ATF7IP（SETDB1的已知结合伴侣）调节。从机制上讲，ATF7IP可能通过与SETDB1的N末端区域结合来抑制其核输出，从而保留SETDB1在核内的保留，SETDB1的N末端区域具有核输出信号基序，并促进其核输入。SETDB1的核定位增加了其泛素化的，酶促活性更高的形式。