Weirich Sara, Khella Mina S, Jeltsch Albert
Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, African Union Organization Street, Abbassia, Cairo 11566, Egypt.
Life (Basel). 2021 Jul 16;11(7):703. doi: 10.3390/life11070703.
SUV39H1 and SUV39H2 were the first protein lysine methyltransferases that were identified more than 20 years ago. Both enzymes introduce di- and trimethylation at histone H3 lysine 9 (H3K9) and have important roles in the maintenance of heterochromatin and gene repression. They consist of a catalytically active SET domain and a chromodomain, which binds H3K9me2/3 and has roles in enzyme targeting and regulation. The heterochromatic targeting of SUV39H enzymes is further enhanced by the interaction with HP1 proteins and repeat-associated RNA. SUV39H1 and SUV39H2 recognize an RKST motif with additional residues on both sides, mainly K4 in the case of SUV39H1 and G12 in the case of SUV39H2. Both SUV39H enzymes methylate different non-histone proteins including RAG2, DOT1L, SET8 and HupB in the case of SUV39H1 and LSD1 in the case of SUV39H2. Both enzymes are expressed in embryonic cells and have broad expression profiles in the adult body. SUV39H1 shows little tissue preference except thymus, while SUV39H2 is more highly expressed in the brain, testis and thymus. Both enzymes are connected to cancer, having oncogenic or tumor-suppressive roles depending on the tumor type. In addition, SUV39H2 has roles in the brain during early neurodevelopment.
SUV39H1和SUV39H2是20多年前最早被鉴定出来的蛋白质赖氨酸甲基转移酶。这两种酶都能在组蛋白H3赖氨酸9（H3K9）上引入二甲基化和三甲基化，在异染色质的维持和基因抑制中发挥重要作用。它们由一个具有催化活性的SET结构域和一个色域组成，该色域与H3K9me2/3结合，在酶的靶向和调节中发挥作用。与HP1蛋白和重复相关RNA的相互作用进一步增强了SUV39H酶对异染色质的靶向作用。SUV39H1和SUV39H2识别一个两侧带有额外残基的RKST基序，对于SUV39H1主要是K4，对于SUV39H2主要是G12。两种SUV39H酶都能使不同的非组蛋白甲基化，对于SUV39H1包括RAG2、DOT1L、SET8和HupB，对于SUV39H2包括LSD1。这两种酶在胚胎细胞中都有表达，在成体中具有广泛的表达谱。除胸腺外，SUV39H1几乎没有组织偏好，而SUV39H2在脑、睾丸和胸腺中表达更高。这两种酶都与癌症有关，根据肿瘤类型具有致癌或抑癌作用。此外，SUV39H2在早期神经发育过程中在脑中发挥作用。
