Unique roles of ATAC and SAGA KAT2A complexes in normal and malignant hematopoiesis

Abstract

Epigenetic histone modifiers are key players in cell fate decisions. Significant research has focused on their enzymatic activity, but less is known about the contextual role of the complexes they integrate. We focus on KAT2A, a histone acetyltransferase we recently associated with leukemia stem cell maintenance, and which participates in ATAC and SAGA complexes. We show that ATAC is uniquely required for maintenance of normal and leukemia stem and progenitor cells, while SAGA more specifically contributes to cell identity. This dichotomy sets a paradigm for investigating epigenetic activities in their macromolecular context and informs epigenetic regulator targeting for translational purposes.