Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein.
Methylation of histone H4 lysine 20 (H4K20me) is essential for recruiting checkpoint proteins 53BP1/Crb2 to DNA lesions and subsequent activation of a DNA-damage checkpoint. In fission yeast, Set9 (spKMT5) catalyzes mono-, di-, and trimethylation of H4K20. However, the mechanisms that regulate Set9 function are poorly understood. Here, we identified a PWWP domain protein Pdp1 as a Set9-associated factor. Pdp1 binds to histones and is required for Set9 chromatin localization. Yeast cells without Pdp1 were deficient in all three states of H4K20me, sensitive to genotoxic treatments, and impaired in Crb2 recruitment. The PWWP domain of Pdp1 binds to H4K20me, and mutations within the PWWP domain that abrogated this interaction in vitro reduced both the association of Set9 with chromatin and the extent of H4K20me in vivo. These results demonstrate that the PWWP domain is a new methyl-lysine recognition motif that plays important roles in epigenetic regulation.
Wang
Yu
Y
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Reddy
Bharat
B
Thompson
James
J
Wang
Hengbin
H
Noma
Ken-ichi
K
Yates
John R
JR
Jia
Songtao
S
D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine