In mammalian cells, the SET1/MLL complexes are the main writers of the H3K4 methyl mark that is associated with active gene expression. The activities of these complexes are critically dependent on the association of the catalytic subunit with their shared core subunits, WDR5, RBBP5, ASH2L, and DPY30, collectively referred as WRAD. In addition, some of these core subunits can bind to proteins other than the SET1/MLL complex components. This review starts with discussion of the molecular activities of these core subunits, with an emphasis on DPY30 in organizing the assembly of the SET1/MLL complexes with other associated factors. This review then focuses on the roles of the core subunits in stem cells and development, as well as in diseased cell states, mainly cancer, and ends with discussion on dissecting the responsible activities of the core subunits and how we may target them for potential disease treatment. This article is part of a Special Issue entitled: The MLL family of proteins in normal development and disease edited by Thomas A Milne.

中文翻译：

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SET1 / MLL复杂核心亚基在发育和疾病中的复杂活动。

在哺乳动物细胞中，SET1 / MLL复合物是与活跃基因表达相关的H3K4甲基标记的主要作者。这些配合物的活性主要取决于催化亚基与其共有的核心亚基WDR5，RBBP5，ASH2L和DPY30的关联，这些总称为WRAD。另外，这些核心亚基中的一些可以与SET1 / MLL复合物成分以外的蛋白质结合。这篇综述从对这些核心亚基的分子活性的讨论开始，重点是DPY30在组织SET1 / MLL复合物与其他相关因素的组装中的作用。然后，本文将重点介绍核心亚基在干细胞和发育以及疾病细胞状态（主要是癌症）中的作用，最后以讨论解剖核心亚基的负责活动以及我们如何针对潜在的疾病治疗为目标进行讨论。本文是《特刊》（Thomas A Milne）编辑的《正常发育和疾病中的MLL蛋白家族》一期的一部分。