PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin.
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.
Nishioka
Kenichi
K
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Rice
Judd C
JC
Sarma
Kavitha
K
Erdjument-Bromage
Hediye
H
Werner
Janis
J
Wang
Yanming
Y
Chuikov
Sergei
S
Valenzuela
Pablo
P
Tempst
Paul
P
Steward
Ruth
R
Lis
John T
JT
Allis
C David
CD
Reinberg
Danny
D
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D011496:Protein Methyltransferases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine