SET Domain Containing Protein 8 (SETD8)

A mutation in Drosophila Pr/set7 was lethal: second instar larval death coincided with the loss of H4-lys20 methylation, indicating a fundamental role for Pr/set7 in development. Transcriptionally competent regions lacked H4-lys20 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-lys16, had significantly decreased levels of lys20 methylation compared with that of females. In vitro, methylation of lys20 and acetylation of lys16 on the H4 tail were competitive. Taken together, these results supported the hypothesis that methylation of H4-lys20 maintains silent chromatin, in part, by precluding neighboring acetylation on the H4 tail.