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 Hsieh, C.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsieh, C.-L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 1999, p. 46-56, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evidence that Protein Binding Specifies Sites of DNA Demethylation

Chih-Lin Hsieh*

Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90033

Received 9 June 1998/Returned for modification 11 August 1998/Accepted 17 September 1998

It has been hypothesized that protein factors may protect CpG islands from methyltransferase during development and that demethylation may involve protein-DNA interactions at demethylated sites. However, direct evidence has been lacking. In this study, demethylation at the EBNA-1 binding sites of the Epstein-Barr virus latent replication origin, oriP, was investigated by using human cells. Several novel findings are discussed. First, there are specific preferential demethylation sites within the oriP region. Second, the DNA sequence of oriP alone is not the target of an active demethylation process. Third, EBNA-1 binding is required for the site-specific demethylation in oriP. Interestingly, CpG sites adjacent to and between the EBNA-1 sites do not become demethylated. Fourth, demethylation of the first DNA strand in oriP at the EBNA-1 binding sites involves a passive (replication-dependent) mechanism. The second-strand demethylation appears to occur through an active mechanism. That is, EBNA-1 protein binding prevents the EBNA-1 binding sites from being remethylated after one round of DNA replication, and it appears that an active demethylase then demethylates these hemimethylated sites. This study provides clear evidence that protein binding specifies sites of DNA demethylation and provides insights into the sequence of steps and the mechanism of demethylation.

* Mailing address: Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, 1441 Eastlake Ave., Room 5420, Norris Cancer Center, Mail Stop #73, Los Angeles, CA 90033. Phone: (323) 865-0567. Fax: (323) 865-3019. E-mail: hsieh_c{at}froggy.hsc.usc.edu.

Molecular and Cellular Biology, January 1999, p. 46-56, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Day, L., Chau, C. M., Nebozhyn, M., Rennekamp, A. J., Showe, M., Lieberman, P. M. (2007). Chromatin Profiling of Epstein-Barr Virus Latency Control Region. J. Virol. 81: 6389-6401 [Abstract] [Full Text]  
  • Webster, R. B., Rodriguez, Y., Klimecki, W. T., Vercelli, D. (2007). The Human IL-13 Locus in Neonatal CD4+ T Cells Is Refractory to the Acquisition of a Repressive Chromatin Architecture. J. Biol. Chem. 282: 700-709 [Abstract] [Full Text]  
  • Kress, C., Thomassin, H., Grange, T. (2006). Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks. Proc. Natl. Acad. Sci. USA 103: 11112-11117 [Abstract] [Full Text]  
  • Chau, C. M., Zhang, X.-Y., McMahon, S. B., Lieberman, P. M. (2006). Regulation of Epstein-Barr Virus Latency Type by the Chromatin Boundary Factor CTCF.. J. Virol. 80: 5723-5732 [Abstract] [Full Text]  
  • Chan, H.-W., Miller, J. S., Moore, M. B., Lutz, C. T. (2005). Epigenetic Control of Highly Homologous Killer Ig-Like Receptor Gene Alleles. J. Immunol. 175: 5966-5974 [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]  
  • Maier, H., Colbert, J., Fitzsimmons, D., Clark, D. R., Hagman, J. (2003). Activation of the Early B-Cell-Specific mb-1 (Ig-{alpha}) Gene by Pax-5 Is Dependent on an Unmethylated Ets Binding Site. Mol. Cell. Biol. 23: 1946-1960 [Abstract] [Full Text]  
  • Chedin, F., Lieber, M. R., Hsieh, C.-L. (2002). The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc. Natl. Acad. Sci. USA 99: 16916-16921 [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]  
  • Cui, H., Fedoroff, N. V. (2002). Inducible DNA Demethylation Mediated by the Maize Suppressor-mutator Transposon-Encoded TnpA Protein. Plant Cell 14: 2883-2899 [Abstract] [Full Text]  
  • Gidekel, S., Bergman, Y. (2002). A Unique Developmental Pattern of Oct-3/4 DNA Methylation Is Controlled by a cis-demodification Element. J. Biol. Chem. 277: 34521-34530 [Abstract] [Full Text]  
  • Tao, Q., Huang, H., Geiman, T. M., Lim, C. Y., Fu, L., Qiu, G.-H., Robertson, K. D. (2002). Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells. Hum Mol Genet 11: 2091-2102 [Abstract] [Full Text]  
  • Hori, N., Nakano, H., Takeuchi, T., Kato, H., Hamaguchi, S., Oshimura, M., Sato, K. (2002). A Dyad Oct-binding Sequence Functions as a Maintenance Sequence for the Unmethylated State within the H19/Igf2-imprinted Control Region. J. Biol. Chem. 277: 27960-27967 [Abstract] [Full Text]  
  • Xie, W., Han, S., Khan, M., DeJong, J. (2002). Regulation of ALF Gene Expression in Somatic and Male Germ Line Tissues Involves Partial and Site-specific Patterns of Methylation. J. Biol. Chem. 277: 17765-17774 [Abstract] [Full Text]  
  • Lin, I. G., Han, L., Taghva, A., O'Brien, L. E., Hsieh, C.-L. (2002). Murine De Novo Methyltransferase Dnmt3a Demonstrates Strand Asymmetry and Site Preference in the Methylation of DNA In Vitro. Mol. Cell. Biol. 22: 704-723 [Abstract] [Full Text]  
  • Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev. 16: 6-21 [Full Text]  
  • Jost, J.-P., Oakeley, E. J., Zhu, B., Benjamin, D., Thiry, S., Siegmann, M., Jost, Y.-C. (2001). 5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation. Nucleic Acids Res 29: 4452-4461 [Abstract] [Full Text]  
  • Benjamin, D., Jost, J.-P. (2001). Reversal of methylation-mediated repression with short-chain fatty acids: evidence for an additional mechanism to histone deacetylation. Nucleic Acids Res 29: 3603-3610 [Abstract] [Full Text]  
  • Viollet, B., Yaniv, M., Pontoglio, M. (2001). Embryonic but Not Postnatal Reexpression of Hepatocyte Nuclear Factor 1{alpha} (HNF1{alpha}) Can Reactivate the Silent Phenylalanine Hydroxylase Gene in HNF1{alpha}-Deficient Hepatocytes. Mol. Cell. Biol. 21: 3662-3670 [Abstract] [Full Text]  
  • Han, L., Lin, I. G., Hsieh, C.-L. (2001). Protein Binding Protects Sites on Stable Episomes and in the Chromosome from De Novo Methylation. Mol. Cell. Biol. 21: 3416-3424 [Abstract] [Full Text]  
  • Costello, J. F, Plass, C. (2001). Methylation matters. J. Med. Genet. 38: 285-303 [Abstract] [Full Text]  
  • Zhu, B., Benjamin, D., Zheng, Y., Angliker, H., Thiry, S., Siegmann, M., Jost, J.-P. (2001). Overexpression of 5-methylcytosine DNA glycosylase in human embryonic kidney cells EcR293 demethylates the promoter of a hormone-regulated reporter gene. Proc. Natl. Acad. Sci. USA 10.1073/pnas.091097298v1 [Abstract] [Full Text]  
  • Salamon, D., Takacs, M., Ujvari, D., Uhlig, J., Wolf, H., Minarovits, J., Niller, H. H. (2001). Protein-DNA Binding and CpG Methylation at Nucleotide Resolution of Latency-Associated Promoters Qp, Cp, and LMP1p of Epstein-Barr Virus. J. Virol. 75: 2584-2596 [Abstract] [Full Text]  
  • Feng, Y.-Q., Lorincz, M. C., Fiering, S., Greally, J. M., Bouhassira, E. E. (2001). Position Effects Are Influenced by the Orientation of a Transgene with Respect to Flanking Chromatin. Mol. Cell. Biol. 21: 298-309 [Abstract] [Full Text]  
  • Schübeler, D., Lorincz, M. C., Cimbora, D. M., Telling, A., Feng, Y.-Q., Bouhassira, E. E., Groudine, M. (2000). Genomic Targeting of Methylated DNA: Influence of Methylation on Transcription, Replication, Chromatin Structure, and Histone Acetylation. Mol. Cell. Biol. 20: 9103-9112 [Abstract] [Full Text]  
  • Lin, I. G., Tomzynski, T. J., Ou, Q., Hsieh, C.-L. (2000). Modulation of DNA Binding Protein Affinity Directly Affects Target Site Demethylation. Mol. Cell. Biol. 20: 2343-2349 [Abstract] [Full Text]  
  • Shin, J.-Y., Kim, H.-S., Park, J., Park, J.-B., Lee, J.-Y. (2000). Mechanism for Inactivation of the KIP Family Cyclin-dependent Kinase Inhibitor Genes in Gastric Cancer Cells. Cancer Res. 60: 262-265 [Abstract] [Full Text]  
  • Hsieh, C.-L. (1999). In Vivo Activity of Murine De Novo Methyltransferases, Dnmt3a and Dnmt3b. Mol. Cell. Biol. 19: 8211-8218 [Abstract] [Full Text]  
  • Wolffe, A. P., Jones, P. L., Wade, P. A. (1999). DNA demethylation. Proc. Natl. Acad. Sci. USA 96: 5894-5896 [Full Text]  
  • Stunkel, W., Ait-Si-Ali, S., Jones, P. L., Wolffe, A. P. (2001). Programming the Transcriptional State of Replicating Methylated DNA. J. Biol. Chem. 276: 20743-20749 [Abstract] [Full Text]  
  • Cervoni, N., Szyf, M. (2001). Demethylase Activity Is Directed by Histone Acetylation. J. Biol. Chem. 276: 40778-40787 [Abstract] [Full Text]  
  • Zhu, B., Benjamin, D., Zheng, Y., Angliker, H., Thiry, S., Siegmann, M., Jost, J.-P. (2001). Overexpression of 5-methylcytosine DNA glycosylase in human embryonic kidney cells EcR293 demethylates the promoter of a hormone-regulated reporter gene. Proc. Natl. Acad. Sci. USA 98: 5031-5036 [Abstract] [Full Text]  
  • Zhu, B., Zheng, Y., Hess, D., Angliker, H., Schwarz, S., Siegmann, M., Thiry, S., Jost, J.-P. (2000). 5-Methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex. Proc. Natl. Acad. Sci. USA 97: 5135-5139 [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»