Borbolla-Vázquez Jessica, Orozco Esther, Medina-Gómez Christian, Martínez-Higuera Aarón, Javier-Reyna Rosario, Chávez Bibiana, Betanzos Abigail, Rodríguez Mario A
Departamento de Infectómica y Patogénesis Molecular. CINVESTAV-IPN. AP. 14-740 México, D.F. México.
Mol Microbiol. 2016 Jul;101(2):351-65. doi: 10.1111/mmi.13394. Epub 2016 May 6.
Lysine methylation of histones, a posttranslational modification catalyzed by lysine methyltransferases (HKMTs), plays an important role in the epigenetic regulation of transcription. Lysine methylation of non-histone proteins also impacts the biological function of proteins. Previously it has been shown that lysine methylation of histones of Entamoeba histolytica, the protozoan parasite that infects 50 million people worldwide each year and causing up to 100,000 deaths annually, is implicated in the epigenetic machinery of this microorganism. However, the identification and characterization of HKMTs in this parasite had not yet been determined. In this work we identified four HKMTs in E. histolytica (EhHKMT1 to EhHKMT4) that are expressed by trophozoites. Enzymatic assays indicated that all of them are able to transfer methyl groups to commercial histones. EhHKMT1, EhHKMT2 and EhHKMT4 were detected in nucleus and cytoplasm of trophozoites. In addition EhHKMT2 and EhHKMT4 were located in vesicles containing ingested cells during phagocytosis, and they co-immunoprecipitated with EhADH, a protein involved in the phagocytosis of this parasite. Results suggest that E. histolytica uses its HKMTs to regulate transcription by epigenetic mechanisms, and at least two of them could also be implicated in methylation of proteins that participate in phagocytosis.
组蛋白赖氨酸甲基化是一种由赖氨酸甲基转移酶（HKMTs）催化的翻译后修饰，在转录的表观遗传调控中发挥着重要作用。非组蛋白的赖氨酸甲基化也会影响蛋白质的生物学功能。此前已有研究表明，溶组织内阿米巴（Entamoeba histolytica）的组蛋白赖氨酸甲基化与该微生物的表观遗传机制有关。溶组织内阿米巴是一种原生动物寄生虫，每年感染全球5000万人，每年导致多达10万人死亡。然而，该寄生虫中HKMTs的鉴定和特征尚未确定。在这项研究中，我们在溶组织内阿米巴中鉴定出四种由滋养体表达的HKMTs（EhHKMT1至EhHKMT4）。酶活性测定表明，它们都能够将甲基转移到商业组蛋白上。在滋养体的细胞核和细胞质中检测到了EhHKMT1、EhHKMT2和EhHKMT4。此外，在吞噬作用过程中，EhHKMT2和EhHKMT4位于含有摄入细胞的小泡中，并且它们与EhADH（一种参与该寄生虫吞噬作用的蛋白质）进行了共免疫沉淀。结果表明，溶组织内阿米巴利用其HKMTs通过表观遗传机制调控转录，并且其中至少两种还可能参与了参与吞噬作用的蛋白质的甲基化。
