This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Melcher, M.
Right arrow Articles by Jenuwein, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Melcher, M.
Right arrow Articles by Jenuwein, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2000, p. 3728-3741, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Structure-Function Analysis of SUV39H1 Reveals a Dominant Role in Heterochromatin Organization, Chromosome Segregation, and Mitotic Progression

Martin Melcher, Manfred Schmid, Louise Aagaard, Philipp Selenko,dagger Götz Laible,Dagger and Thomas Jenuwein*

Research Institute of Molecular Pathology, The Vienna Biocenter, A-1030 Vienna, Austria

Received 10 November 1999/Returned for modification 21 December 1999/Accepted 19 February 2000

SUV39H1, a human homologue of the Drosophila position effect variegation modifier Su(var)3-9 and of the Schizosaccharomyces pombe silencing factor clr4, encodes a novel heterochromatic protein that transiently accumulates at centromeric positions during mitosis. Using a detailed structure-function analysis of SUV39H1 mutant proteins in transfected cells, we now show that deregulated SUV39H1 interferes at multiple levels with mammalian higher-order chromatin organization. First, forced expression of full-length SUV39H1 (412 amino acids) redistributes endogenous M31 (HP1beta ) and induces abundant associations with inter- and metaphase chromatin. These properties depend on the C-terminal SET domain, although the major portion of the SUV39H1 protein (amino acids 89 to 412) does not display affinity for nuclear chromatin. By contrast, the M31 interaction surface, which was mapped to the first 44 N-terminal amino acids, together with the immediately adjacent chromo domain, directs specific accumulation at heterochromatin. Second, cells overexpressing full-length SUV39H1 display severe defects in mitotic progression and chromosome segregation. Surprisingly, whereas localization of centromere proteins is unaltered, the focal, G2-specific distribution of phosphorylated histone H3 at serine 10 (phosH3) is dispersed in these cells. This phosH3 shift is not observed with C-terminally truncated mutant SUV39H1 proteins or with deregulated M31. Together, our data reveal a dominant role(s) for the SET domain of SUV39H1 in the distribution of prominent heterochromatic proteins and suggest a possible link between a chromosomal SU(VAR) protein and histone H3.

* Corresponding author. Mailing address: Research Institute of Molecular Pathology, The Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria. Phone: 43-1-797-30-474. Fax: 43-1-798-7153. E-mail: jenuwein{at}nt.imp.univie.ac.at.

dagger Present address: EMBL, D-69117 Heidelberg, Germany.

Dagger Present address: Dairy Science Group, AgResearch, Hamilton, New Zealand.

Molecular and Cellular Biology, May 2000, p. 3728-3741, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • LeRoy, G., Weston, J. T., Zee, B. M., Young, N. L., Plazas-Mayorca, M. D., Garcia, B. A. (2009). Heterochromatin Protein 1 Is Extensively Decorated with Histone Code-like Post-translational Modifications. Mol. Cell. Proteomics 8: 2432-2442 [Abstract] [Full Text]  
  • Heit, R., Rattner, J. B., Chan, G. K. T., Hendzel, M. J. (2009). G2 histone methylation is required for the proper segregation of chromosomes. J. Cell Sci. 122: 2957-2968 [Abstract] [Full Text]  
  • Scharf, A. N. D., Barth, T. K., Imhof, A. (2009). Establishment of Histone Modifications after Chromatin Assembly. Nucleic Acids Res 37: 5032-5040 [Abstract] [Full Text]  
  • Zhou, J., Wang, Q., Chen, L.-L., Carmichael, G. G. (2008). On the mechanism of induction of heterochromatin by the RNA-binding protein vigilin. RNA 14: 1773-1781 [Abstract] [Full Text]  
  • Ritchie, K., Seah, C., Moulin, J., Isaac, C., Dick, F., Berube, N. G. (2008). Loss of ATRX leads to chromosome cohesion and congression defects. JCB 180: 315-324 [Abstract] [Full Text]  
  • Nishida, M., Kato, M., Kato, Y., Sasai, N., Ueda, J., Tachibana, M., Shinkai, Y., Yamaguchi, M. (2007). Identification of ZNF200 as a novel binding partner of histone H3 methyltransferase G9a. GENES CELLS 12: 877-888 [Abstract] [Full Text]  
  • Kwon, Y.-S., Garcia-Bassets, I., Hutt, K. R., Cheng, C. S., Jin, M., Liu, D., Benner, C., Wang, D., Ye, Z., Bibikova, M., Fan, J.-B., Duan, L., Glass, C. K., Rosenfeld, M. G., Fu, X.-D. (2007). Sensitive ChIP-DSL technology reveals an extensive estrogen receptor {alpha}-binding program on human gene promoters. Proc. Natl. Acad. Sci. USA 104: 4852-4857 [Abstract] [Full Text]  
  • Clough, E., Moon, W., Wang, S., Smith, K., Hazelrigg, T. (2007). Histone methylation is required for oogenesis in Drosophila. Development 134: 157-165 [Abstract] [Full Text]  
  • Monier, K., Mouradian, S., Sullivan, K. F. (2007). DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomains. J. Cell Sci. 120: 101-114 [Abstract] [Full Text]  
  • Ting, A. H., McGarvey, K. M., Baylin, S. B. (2006). The cancer epigenome--components and functional correlates. Genes Dev. 20: 3215-3231 [Abstract] [Full Text]  
  • Reeves, M., Murphy, J., Greaves, R., Fairley, J., Brehm, A., Sinclair, J. (2006). Autorepression of the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer at Late Times of Infection Is Mediated by the Recruitment of Chromatin Remodeling Enzymes by IE86.. J. Virol. 80: 9998-10009 [Abstract] [Full Text]  
  • Bradley, S. P., Kaminski, D. A., Peters, A. H. F. M., Jenuwein, T., Stavnezer, J. (2006). The Histone Methyltransferase Suv39h1 Increases Class Switch Recombination Specifically to IgA. J. Immunol. 177: 1179-1188 [Abstract] [Full Text]  
  • McManus, K. J., Biron, V. L., Heit, R., Underhill, D. A., Hendzel, M. J. (2006). Dynamic Changes in Histone H3 Lysine 9 Methylations: IDENTIFICATION OF A MITOSIS-SPECIFIC FUNCTION FOR DYNAMIC METHYLATION IN CHROMOSOME CONGRESSION AND SEGREGATION. J. Biol. Chem. 281: 8888-8897 [Abstract] [Full Text]  
  • Carbone, R., Botrugno, O. A., Ronzoni, S., Insinga, A., Di Croce, L., Pelicci, P. G., Minucci, S. (2006). Recruitment of the Histone Methyltransferase SUV39H1 and Its Role in the Oncogenic Properties of the Leukemia-Associated PML-Retinoic Acid Receptor Fusion Protein. Mol. Cell. Biol. 26: 1288-1296 [Abstract] [Full Text]  
  • Krouwels, I. M., Wiesmeijer, K., Abraham, T. E., Molenaar, C., Verwoerd, N. P., Tanke, H. J., Dirks, R. W. (2005). A glue for heterochromatin maintenance: stable SUV39H1 binding to heterochromatin is reinforced by the SET domain. JCB 170: 537-549 [Abstract] [Full Text]  
  • Stewart, M. D., Li, J., Wong, J. (2005). Relationship between Histone H3 Lysine 9 Methylation, Transcription Repression, and Heterochromatin Protein 1 Recruitment. Mol. Cell. Biol. 25: 2525-2538 [Abstract] [Full Text]  
  • Boulias, K., Talianidis, I. (2004). Functional role of G9a-induced histone methylation in small heterodimer partner-mediated transcriptional repression. Nucleic Acids Res 32: 6096-6103 [Abstract] [Full Text]  
  • Nishio, H., Walsh, M. J. (2004). CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription. Proc. Natl. Acad. Sci. USA 101: 11257-11262 [Abstract] [Full Text]  
  • Sakakibara, S., Ueda, K., Nishimura, K., Do, E., Ohsaki, E., Okuno, T., Yamanishi, K. (2004). Accumulation of Heterochromatin Components on the Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus Mediated by the Latency-Associated Nuclear Antigen. J. Virol. 78: 7299-7310 [Abstract] [Full Text]  
  • FRANCO, A.A., KAUFMAN, P.D. (2004). Histone Deposition Proteins: Links between the DNA Replication Machinery and Epigenetic Gene Silencing. Cold Spring Harb Symp Quant Biol 69: 201-208 [Abstract]  
  • Greil, F., van der Kraan, I., Delrow, J., Smothers, J. F., de Wit, E., Bussemaker, H. J., van Driel, R., Henikoff, S., van Steensel, B. (2003). Distinct HP1 and Su(var)3-9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location. Genes Dev. 17: 2825-2838 [Abstract] [Full Text]  
  • Weissmann, F., Muyrers-Chen, I., Musch, T., Stach, D., Wiessler, M., Paro, R., Lyko, F. (2003). DNA Hypermethylation in Drosophila melanogaster Causes Irregular Chromosome Condensation and Dysregulation of Epigenetic Histone Modifications. Mol. Cell. Biol. 23: 2577-2586 [Abstract] [Full Text]  
  • Sewalt, R. G. A. B., Lachner, M., Vargas, M., Hamer, K. M., den Blaauwen, J. L., Hendrix, T., Melcher, M., Schweizer, D., Jenuwein, T., Otte, A. P. (2002). Selective Interactions between Vertebrate Polycomb Homologs and the SUV39H1 Histone Lysine Methyltransferase Suggest that Histone H3-K9 Methylation Contributes to Chromosomal Targeting of Polycomb Group Proteins. Mol. Cell. Biol. 22: 5539-5553 [Abstract] [Full Text]  
  • Urnov, F. D. (2002). Methylation and the Genome: the Power of a Small Amendment. J. Nutr. 132: 2450S-2456 [Abstract] [Full Text]  
  • Filesi, I., Cardinale, A., van der Sar, S., Cowell, I. G., Singh, P. B., Biocca, S. (2002). Loss of Heterochromatin Protein 1 (HP1) chromodomain function in mammalian cells by intracellular antibodies causes cell death. J. Cell Sci. 115: 1803-1813 [Abstract] [Full Text]  
  • Jenuwein, T., Allis, C. D. (2001). Translating the Histone Code. Science 293: 1074-1080 [Abstract] [Full Text]  
  • Hari, K. L., Cook, K. R., Karpen, G. H. (2001). The Drosophila Su(var)2-10 locus regulates chromosome structure and function and encodes a member of the PIAS protein family. Genes Dev. 15: 1334-1348 [Abstract] [Full Text]  
  • Zeitlin, S., Barber, C., Allis, C., Sullivan, K (2001). Differential regulation of CENP-A and histone H3 phosphorylation in G2/M. J. Cell Sci. 114: 653-661 [Abstract]  
  • O'Carroll, D., Scherthan, H., Peters, A. H. F. M., Opravil, S., Haynes, A. R., Laible, G., Rea, S., Schmid, M., Lebersorger, A., Jerratsch, M., Sattler, L., Mattei, M. G., Denny, P., Brown, S. D. M., Schweizer, D., Jenuwein, T. (2000). Isolation and Characterization of Suv39h2, a Second Histone H3 Methyltransferase Gene That Displays Testis-Specific Expression. Mol. Cell. Biol. 20: 9423-9433 [Abstract] [Full Text]  
  • Firestein, R., Cui, X., Huie, P., Cleary, M. L. (2000). Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9. Mol. Cell. Biol. 20: 4900-4909 [Abstract] [Full Text]  
  • Tachibana, M., Sugimoto, K., Fukushima, T., Shinkai, Y. (2001). SET Domain-containing Protein, G9a, Is a Novel Lysine-preferring Mammalian Histone Methyltransferase with Hyperactivity and Specific Selectivity to Lysines 9 and 27 of Histone H3. J. Biol. Chem. 276: 25309-25317 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»