The complex activities of the SET1/MLL complex core subunits in development and disease

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.