Despite strong engagement of HRP2′s PWWP domain with H3K36me2/3, Baude et al. reported that endogenous HRP2 has a high affinity for repressive histone marks, including H3K9me3 and H3K27me3, in U2OS osteosarcoma cells, suggesting that HRP2 activity is not limited to euchromatic regions and genomic location of this protein could be cell-type specific [25]. The gene discussed is HDGFL2; the disease is osteosarcoma.