Supplementary Experimental Procedures

The methyl-K79-specific antibody was raised by injection of rabbits with a synthetic peptide coding for amino acids 73–83 of histone H3 with K79 dimethylated (IAQDFmKTDLRF). The methyl-K4,-K9 antibodies were purchased from Upstate Biotechnology. The full-length hDOT1L was derived from two overlapping EST clones: BF507396 and BF982417. The Flag-tagged constructs were cloned into the EcoRI/XhoI sites of a pcDNA-derived vector by PCR. The GST-fusion of the hDOT1L N-terminal fragments were also cloned into the EcoRI/XhoI sites of pGEX-KG vector by PCR. The mutants were generated through PCR-based mutagenesis. All PCR-gener-ated constructs were verified by sequencing. The GST-hDOT1L fu-sion proteins were purified as previously described [S1]. The recom-binant proteins were then cleaved using thrombin following manufacturer’s instructions. Proteins were quantitated by Coomas-sie staining