The KMT9α/KMT9ß core complex, hereafter named KMT9 is a novel histone methyltransferase writing the chromatin mark H4K12me. KMT9 loss results in reduced H4K12me levels and impaired proliferation of prostate cancer. In human normal prostate KMT9 is localized in the cytoplasm but dynamically shifts in the nucleus as tumorigenesis progresses. In vivo, KMT9 forms the core subunit of a multi-protein assembly. We propose to (1) analyze the components and structural requirements necessary for KMT9 machinery assembly. We shall (2) identify signaling pathways regulating KMT9 subcellular localization, assembly, and function.