Yang Weiwei, Ernst Patricia
Department of Pediatrics and Pharmacology, University of Colorado, Denver/Anschutz Medical Campus, Aurora, CO, 80045, USA.
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
Int J Hematol. 2017 Jan;105(1):7-16. doi: 10.1007/s12185-016-2118-8. Epub 2016 Oct 31.
Accumulating recent evidence supports the notion that many enzymes that modify histones are fundamental players in normal hematopoiesis as well as hematologic malignancies, and represent an important new class of drug targets. Histone H3 lysine 4 (H3K4) methylation plays several distinct roles in gene expression and is modulated by specific methyltransferases and demethylases. Recent progress has been made clarifying the unique biological roles of the enzymes that carry out H3K4 methylation, yet a detailed understanding of H3K4 methylation states in various genomic contexts and the diverse functions of the enzymes that perform these methylation events is incomplete, but developing rapidly. In this review, we summarize and discuss the general mechanisms of H3K4 methylation, and how the six main enzymes from the SET/MLL family (responsible for H3K4me1/me2/me3) function in hematopoiesis and in hematologic malignancies.
最近越来越多的证据支持这样一种观点，即许多修饰组蛋白的酶是正常造血以及血液系统恶性肿瘤的基本参与者，并且代表了一类重要的新型药物靶点。组蛋白H3赖氨酸4（H3K4）甲基化在基因表达中发挥多种不同作用，并受到特定甲基转移酶和去甲基酶的调节。在阐明进行H3K4甲基化的酶的独特生物学作用方面已取得了最新进展，然而，对各种基因组背景下H3K4甲基化状态以及执行这些甲基化事件的酶的多种功能的详细了解仍不完整，但正在迅速发展。在这篇综述中，我们总结并讨论了H3K4甲基化的一般机制，以及SET/MLL家族中的六种主要酶（负责H3K4me1/me2/me3）在造血和血液系统恶性肿瘤中的作用。
