Early on, our group employed conditional knockout approaches to discover that hematopoietic stem cells (HSCs) and pre-B cells are particularly sensitive to MLL1 levels for homeostasis (PMIDs 18371366, 29351999). We employed genomic and genetic methods to identify key target genes of MLL1 and have studied the role of Menin as a partner in regulating target genes in these cell types. Our work showed that Menin and MLL1 regulate largely distinct gene sets during normal blood cell differentiation (PMIDs 23908472 & 30315824). Mechanistic studies illustrate that the MLL1 protein complex likely regulates important HSC genes through its association with a histone acetyltransferases, rather than through its own histone methyltransferase activity (PMID24813891) (Figure). We have also contributed to work targeting and understanding other epigenetic regulators such as Ash1L, SETBP1 and EZH2 (PMIDs 40044670, 33990599 and 35036869 and unpublished).