HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 18, 12085-12092, May 2, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/18/12085    most recent M707974200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, H. Articles by Mizzen, C. A. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Mizzen, C. A. Social Bookmarking                      What's this?

Preferential Dimethylation of Histone H4 Lysine 20 by Suv4-20^*

Hongbo Yang, James J. Pesavento¹, Taylor W. Starnes, Diane E. Cryderman^¶, Lori L. Wallrath^¶, Neil L. Kelleher^||**, and Craig A. Mizzen^**2

From the Department of Cell and Developmental Biology, the Center for Biophysics and Computational Biology, the ^||Department of Chemistry, and the ^**Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801 and the ^¶Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242

Post-translational modifications of histone tails direct nuclear processes including transcription, DNA repair, and chromatin packaging. Lysine 20 of histone H4 is mono-, di-, or trimethylated in vivo, but the regulation and significance of these methylations is poorly understood. The SET domain proteins PR-Set7 and Suv4-20 have been implicated in mono- and trimethylation, respectively; however, enzymes that dimethylate lysine 20 have not been identified. Here we report that Drosophila Suv4-20 is a mixed product specificity methyltransferase that dimethylates 90% and trimethylates less than 5% of total H4 at lysine 20 in S2 cells. Trimethylation, but not dimethylation, is reduced in Drosophila larvae lacking HP1, suggesting that an interaction with HP1 regulates the product specificity of Suv4-20 and enrichment of trimethyllysine 20 within heterochromatin. Similar to the Drosophila enzyme, human Suv4-20h1/h2 enzymes generate di- and trimethyllysine 20. PR-Set7 and Suv4-20 are both required for normal levels of methylation, suggesting they have non-redundant functions. Alterations in the level of lysine 20 methylation following knock-down or overexpression of Suv4-20 did not affect lysine 16 acetylation, revealing that these two modifications are not competitive in vivo. Depletion of Suv4-20h1/h2 in HeLa cells impaired the formation of 53BP1 foci, suggesting dimethyllysine 20 is required for a proper DNA damage response. Collectively, the data indicate that Suv4-20 generates nearly ubiquitous dimethylation that facilitates the DNA damage response and selective trimethylation that is involved in heterochromatin formation.

Received for publication, September 24, 2007 , and in revised form, February 7, 2008.

^* This work was supported in part by Grant 04-76 from the Roy J. Carver Charitable Trust and Basil O'Connor Scholar Award FY05-1232 from the March of Dimes (to C. A. M.), Grant GM 61513 from the National Institutes of Health (to L. L. W.), and the Packard Foundation, the Sloan Foundation, a Cottrell Scholar Award, and National Institutes of Health Grant GM 067193-06 (to N. L. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2 and Tables S1 and S2.

¹ Recipient of a National Institutes of Health Institutional NRSA Grant in Molecular Biophysics (5T32 GM 08276).

² To whom correspondence should be addressed: B107 CLSL, MC123, 601 S. Goodwin Ave. Urbana, IL 61801. Tel.: 217-244-4896; Fax: 217-244-1648; E-mail: cmizzen{at}life.uiuc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. T. Greeson, R. Sengupta, A. R. Arida, T. Jenuwein, and S. L. Sanders Di-methyl H4 Lysine 20 Targets the Checkpoint Protein Crb2 to Sites of DNA Damage J. Biol. Chem., November 28, 2008; 283(48): 33168 - 33174. [Abstract] [Full Text] [PDF]

				G. Schotta, R. Sengupta, S. Kubicek, S. Malin, M. Kauer, E. Callen, A. Celeste, M. Pagani, S. Opravil, I. A. De La Rosa-Velazquez, et al. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse Genes & Dev., August 1, 2008; 22(15): 2048 - 2061. [Abstract] [Full Text] [PDF]

				S. I. Houston, K. J. McManus, M. M. Adams, J. K. Sims, P. B. Carpenter, M. J. Hendzel, and J. C. Rice Catalytic Function of the PR-Set7 Histone H4 Lysine 20 Monomethyltransferase Is Essential for Mitotic Entry and Genomic Stability J. Biol. Chem., July 11, 2008; 283(28): 19478 - 19488. [Abstract] [Full Text] [PDF]