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PMID: 19250904 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein.

Molecular cell ·Vol. 33 ·No. 4 ·2009-02-27 ·Pages 428-37

Wang Y, Reddy B, Thompson J, Wang H, Noma K, Yates JR, Jia S

Abstract

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.

MeSH Terms
Amino Acid Sequence Chromatin/metabolism Chromosomal Proteins, Non-Histone/genetics,metabolism DNA Damage Histone Methyltransferases Histone-Lysine N-Methyltransferase Histones/metabolism Lysine/metabolism Mass Spectrometry Methylation Molecular Sequence Data Mutation Protein Methyltransferases/genetics,metabolism Protein Structure, Tertiary Schizosaccharomyces/genetics,metabolism Schizosaccharomyces pombe Proteins/genetics,metabolism
Chemicals
Chromatin Chromosomal Proteins, Non-Histone Histones Schizosaccharomyces pombe Proteins Histone Methyltransferases Protein Methyltransferases Histone-Lysine N-Methyltransferase Lysine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang Yu
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Reddy Bharat
Thompson James
Wang Hengbin
Noma Ken-ichi
Yates John R
Jia Songtao
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2009.02.002
Published
2009-02-27
Pages
428-37
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2673476
Subset
IM
Grants
NIGMS NIH HHS · R01 GM085145-01 · United States
NCRR NIH HHS · P41 RR011823-128195 · United States
NCRR NIH HHS · P41 RR011823 · United States
NCRR NIH HHS · P41 RR11823 · United States
NIGMS NIH HHS · R01 GM085145 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2009.02.002 PMC Full Text View journal details
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