We have purified a human histone H4 lysine 20 methyltransferase and cloned the 
encoding gene, PR/SET07. A mutation in Drosophila pr-set7 is lethal: second 
instar larval death coincides with the loss of H4 lysine 20 methylation, 
indicating a fundamental role for PR-Set7 in development. Transcriptionally 
competent regions lack H4 lysine 20 methylation, but the modification coincided 
with condensed chromosomal regions on polytene chromosomes, including 
chromocenter and euchromatic arms. The Drosophila male X chromosome, which is 
hyperacetylated at H4 lysine 16, has significantly decreased levels of lysine 20 
methylation compared to that of females. In vitro, methylation of lysine 20 and 
acetylation of lysine 16 on the H4 tail are competitive. Taken together, these 
results support the hypothesis that methylation of H4 lysine 20 maintains silent 
chromatin, in part, by precluding neighboring acetylation on the H4 tail.