Department of Biology, Syracuse University, Syracuse, NY 13244, USA.
FEBS J. 2010 Apr;277(8):1832-42. doi: 10.1111/j.1742-4658.2010.07609.x. Epub 2010 Mar 4.
Several acute lymphoblastic and myelogenous leukemias are correlated with alterations in the human mixed lineage leukemia protein-1 (MLL1) gene. MLL1 is a member of the evolutionarily conserved SET1 family of histone H3 lysine 4 (H3K4) methyltransferases, which are required for the regulation of distinct groups of developmentally regulated genes in metazoans. Despite the important biological role of SET1 family enzymes and their involvement in human leukemias, relatively little is understood about how these enzymes work. Here we review several recent structural and biochemical studies that are beginning to shed light on the molecular mechanisms for the regulation of H3K4 methylation by the human MLL1 enzyme.
几种急性淋巴细胞性和髓性白血病与人类混合谱系白血病蛋白-1(MLL1)基因的改变有关。MLL1 是进化上保守的 SET1 家族组蛋白 H3 赖氨酸 4(H3K4)甲基转移酶的成员,对于后生动物中不同发育调控基因群的调控是必需的。尽管 SET1 家族酶具有重要的生物学作用并且它们参与人类白血病,但对于这些酶如何发挥作用的了解相对较少。在这里,我们综述了几项最近的结构和生化研究,这些研究开始揭示人类 MLL1 酶调控 H3K4 甲基化的分子机制。