A novel histone methyltransferase, termed Set9, was isolated from human cells. 
Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 
methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates 
transcription activation. The histone H3 tail interacts specifically with the 
histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes 
the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs 
Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9 
and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9 
by the histone methyltransferase G9a was not affected by Set9 methylation of 
H3-K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in 
transcription activation by competing with histone deacetylases and by 
precluding H3-K9 methylation by Suv39h1. Our results suggest that the 
methylation of histone tails can have distinct effects on transcription, 
depending on its chromosomal location, the combination of posttranslational 
modifications, and the enzyme (or protein complex) involved in the particular 
modification.