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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Lorincz, M. C.
Right arrow Articles by Groudine, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lorincz, M. C.
Right arrow Articles by Groudine, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2001, p. 7913-7922, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.7913-7922.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Methylation-Mediated Proviral Silencing Is Associated with MeCP2 Recruitment and Localized Histone H3 Deacetylation

Matthew C. Lorincz,1 Dirk Schübeler,1 and Mark Groudine1,2,*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 and Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington 981952

Received 31 May 2001/Returned for modification 3 August 2001/Accepted 22 August 2001

The majority of 5-methylcytosine in mammalian DNA resides in endogenous transposable elements and is associated with the transcriptional silencing of these parasitic elements. Methylation also plays an important role in the silencing of exogenous retroviruses. One of the difficulties inherent in the study of proviral silencing is that the sites in which proviruses randomly integrate influence the probability of de novo methylation and expression. In order to compare methylated and unmethylated proviruses at the same genomic site, we used a recombinase-based targeting approach to introduce an in vitro methylated or unmethylated Moloney murine leukemia-based provirus in MEL cells. The methylated and unmethylated states are maintained in vivo, with the exception of the initially methylated proviral enhancer, which becomes demethylated in vivo. Although the enhancer is unmethylated and remodeled, the methylated provirus is transcriptionally silent. To further analyze the repressed state, histone acetylation status was determined by chromatin immunoprecipitation (ChIP) analyses, which revealed that localized histone H3 but not histone H4 hyperacetylation is inversely correlated with proviral methylation density. Since members of the methyl-CpG binding domain (MBD) family of proteins recruit histone deacetylase activity, these proteins may play a role in proviral repression. Interestingly, only MBD3 and MeCP2 are expressed in MEL cells. ChIPs with antibodies specific for these proteins revealed that only MeCP2 associates with the provirus in a methylation-dependent manner. Taken together, our results suggest that MeCP2 recruitment to a methylated provirus is sufficient for transcriptional silencing, despite the presence of a remodeled enhancer.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, A3-025, Seattle, WA 98109. Phone: (206) 667-4497. Fax: (206) 667-5894. E-mail: markg{at}fhcrc.org.

Molecular and Cellular Biology, December 2001, p. 7913-7922, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.7913-7922.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Burns, W. R., Zheng, Z., Rosenberg, S. A., Morgan, R. A. (2009). Lack of specific {gamma}-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation. Blood 114: 2888-2899 [Abstract] [Full Text]  
  • Maksakova, I. A., Zhang, Y., Mager, D. L. (2009). Preferential Epigenetic Suppression of the Autonomous MusD over the Nonautonomous ETn Mouse Retrotransposons. Mol. Cell. Biol. 29: 2456-2468 [Abstract] [Full Text]  
  • Garrison, B. S., Yant, S. R., Mikkelsen, J. G., Kay, M. A. (2007). Postintegrative Gene Silencing within the Sleeping Beauty Transposition System. Mol. Cell. Biol. 27: 8824-8833 [Abstract] [Full Text]  
  • Yasui, D. H., Peddada, S., Bieda, M. C., Vallero, R. O., Hogart, A., Nagarajan, R. P., Thatcher, K. N., Farnham, P. J., LaSalle, J. M. (2007). Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc. Natl. Acad. Sci. USA 104: 19416-19421 [Abstract] [Full Text]  
  • Katz, R. A., Jack-Scott, E., Narezkina, A., Palagin, I., Boimel, P., Kulkosky, J., Nicolas, E., Greger, J. G., Skalka, A. M. (2007). High-Frequency Epigenetic Repression and Silencing of Retroviruses Can Be Antagonized by Histone Deacetylase Inhibitors and Transcriptional Activators, but Uniform Reactivation in Cell Clones Is Restricted by Additional Mechanisms. J. Virol. 81: 2592-2604 [Abstract] [Full Text]  
  • Ding, Y., Wang, X., Su, L., Zhai, J., Cao, S., Zhang, D., Liu, C., Bi, Y., Qian, Q., Cheng, Z., Chu, C., Cao, X. (2007). SDG714, a Histone H3K9 Methyltransferase, Is Involved in Tos17 DNA Methylation and Transposition in Rice. Plant Cell 19: 9-22 [Abstract] [Full Text]  
  • Galvao, T. C., Thomas, J. O. (2005). Structure-specific binding of MeCP2 to four-way junction DNA through its methyl CpG-binding domain. Nucleic Acids Res 33: 6603-6609 [Abstract] [Full Text]  
  • Fish, J. E., Matouk, C. C., Rachlis, A., Lin, S., Tai, S. C., D'Abreo, C., Marsden, P. A. (2005). The Expression of Endothelial Nitric-oxide Synthase Is Controlled by a Cell-specific Histone Code. J. Biol. Chem. 280: 24824-24838 [Abstract] [Full Text]  
  • Tong, Y., Aune, T., Boothby, M. (2005). T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-{gamma} promoter via a conserved T-box half-site. Proc. Natl. Acad. Sci. USA 102: 2034-2039 [Abstract] [Full Text]  
  • Escher, G., Hoang, A., Georges, S., Tchoua, U., El-Osta, A., Krozowski, Z., Sviridov, D. (2005). Demethylation using the epigenetic modifier, 5-azacytidine, increases the efficiency of transient transfection of macrophages. J. Lipid Res. 46: 356-365 [Abstract] [Full Text]  
  • Kim, M., Trinh, B. N., Long, T. I., Oghamian, S., Laird, P. W. (2004). Dnmt1 deficiency leads to enhanced microsatellite instability in mouse embryonic stem cells. Nucleic Acids Res 32: 5742-5749 [Abstract] [Full Text]  
  • Kriaucionis, S., Bird, A. (2004). The major form of MeCP2 has a novel N-terminus generated by alternative splicing. Nucleic Acids Res 32: 1818-1823 [Abstract] [Full Text]  
  • DeMarco, R., Kowaltowski, A. T., Machado, A. A., Soares, M. B., Gargioni, C., Kawano, T., Rodrigues, V., Madeira, A. M. B. N., Wilson, R. A., Menck, C. F. M., Setubal, J. C., Dias-Neto, E., Leite, L. C. C., Verjovski-Almeida, S. (2004). Saci-1, -2, and -3 and Perere, Four Novel Retrotransposons with High Transcriptional Activities from the Human Parasite Schistosoma mansoni. J. Virol. 78: 2967-2978 [Abstract] [Full Text]  
  • Swindle, C. S., Kim, H. G., Klug, C. A. (2004). Mutation of CpGs in the Murine Stem Cell Virus Retroviral Vector Long Terminal Repeat Represses Silencing in Embryonic Stem Cells. J. Biol. Chem. 279: 34-41 [Abstract] [Full Text]  
  • Carvin, C. D., Parr, R. D., Kladde, M. P. (2003). Site-selective in vivo targeting of cytosine-5 DNA methylation by zinc-finger proteins. Nucleic Acids Res 31: 6493-6501 [Abstract] [Full Text]  
  • Yao, S., Osborne, C. S., Bharadwaj, R. R., Pasceri, P., Sukonnik, T., Pannell, D., Recillas-Targa, F., West, A. G., Ellis, J. (2003). Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Res 31: 5317-5323 [Abstract] [Full Text]  
  • Zhao, X., Ueba, T., Christie, B. R., Barkho, B., McConnell, M. J., Nakashima, K., Lein, E. S., Eadie, B. D., Willhoite, A. R., Muotri, A. R., Summers, R. G., Chun, J., Lee, K.-F., Gage, F. H. (2003). Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proc. Natl. Acad. Sci. USA 100: 6777-6782 [Abstract] [Full Text]  
  • Chen, H., Toyooka, S., Gazdar, A. F., Hsieh, J.-T. (2003). Epigenetic Regulation of a Novel Tumor Suppressor Gene (hDAB2IP) in Prostate Cancer Cell Lines. J. Biol. Chem. 278: 3121-3130 [Abstract] [Full Text]  
  • Ghoshal, K., Datta, J., Majumder, S., Bai, S., Dong, X., Parthun, M., Jacob, S. T. (2002). Inhibitors of Histone Deacetylase and DNA Methyltransferase Synergistically Activate the Methylated Metallothionein I Promoter by Activating the Transcription Factor MTF-1 and Forming an Open Chromatin Structure. Mol. Cell. Biol. 22: 8302-8319 [Abstract] [Full Text]  
  • Lunyak, V. V., Burgess, R., Prefontaine, G. G., Nelson, C., Sze, S.-H., Chenoweth, J., Schwartz, P., Pevzner, P. A., Glass, C., Mandel, G., Rosenfeld, M. G. (2002). Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes. Science 298: 1747-1752 [Abstract] [Full Text]  
  • Lorincz, M. C., Schubeler, D., Hutchinson, S. R., Dickerson, D. R., Groudine, M. (2002). DNA Methylation Density Influences the Stability of an Epigenetic Imprint and Dnmt3a/b-Independent De Novo Methylation. Mol. Cell. Biol. 22: 7572-7580 [Abstract] [Full Text]  
  • Koizume, S., Tachibana, K., Sekiya, T., Hirohashi, S., Shiraishi, M. (2002). Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells. Nucleic Acids Res 30: 4770-4780 [Abstract] [Full Text]  
  • Bane, T. K., LeBlanc, J. F., Lee, T. D., Riggs, A. D. (2002). DNA affinity capture and protein profiling by SELDI-TOF mass spectrometry: effect of DNA methylation. Nucleic Acids Res 30: e69-e69 [Abstract] [Full Text]  
  • Suh, Y.-A., Lee, H.-Y., Virmani, A., Wong, J., Mann, K. K., Miller, W. H. Jr., Gazdar, A., Kurie, J. M. (2002). Loss of Retinoic Acid Receptor {beta} Gene Expression Is Linked to Aberrant Histone H3 Acetylation in Lung Cancer Cell Lines. Cancer Res. 62: 3945-3949 [Abstract] [Full Text]  
  • El-Osta, A., Kantharidis, P., Zalcberg, J. R., Wolffe, A. P. (2002). Precipitous Release of Methyl-CpG Binding Protein 2 and Histone Deacetylase 1 from the Methylated Human Multidrug Resistance Gene (MDR1) on Activation. Mol. Cell. Biol. 22: 1844-1857 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»