Rice and coworkers reported a specific and direct binding of SETD8 with the Riz1/PRDM2/KMT8 tumor suppressor and showed that the N-terminal domain of PRDM2 preferentially monomethylates H3K9, thus establishing a H4K20me1-H3K9me1 trans-tail “histone code” [70, 71]. Here, PRDM2 is linked to neoplasm.