Patent ID: 8911933

Claim:
A method of identifying a compound that modulates DOT1L histone H3 lysine 79 (H3-K79) methyltransferase activity, comprising: contacting a DOT1L polypeptide with a nucleosome substrate comprising histone H3 in the presence of a test compound; wherein the DOT1L polypeptide comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:2; (b) an amino acid sequence having at least 95% amino acid sequence similarity with the amino acid sequence of SEQ ID NO:2, wherein said DOT1L polypeptide has H3-K79 methyltransferase activity; and (c) a functional fragment of at least 400 amino acids of the amino acid sequence of (a) or (b) above, wherein said functional fragment comprises a DOT1L histone methyltransferase catalytic domain and has H3-K79 methyltransferase activity; detecting the level of H3-K79 methylation of the nucleosome substrate under conditions sufficient to provide H3-K79 methylation, wherein an elevation or reduction in H3-K79 methylation in the presence of the test compound as compared with the level of histone H3-K79 methylation in the absence of the test compound indicates that the test compound modulates DOT1L H3-K79 methyltransferase activity.