Skip Navigation



Nucleic Acids Research Advance Access published online on December 20, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl1053
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2499K) Freely available
Right arrow Screen PDF (735K) Freely available
Right arrowOA All Versions of this Article:
35/3/740    most recent
gkl1053v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email 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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Smith, A. E.
Right arrow Articles by Ford, K. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, A. E.
Right arrow Articles by Ford, K. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

Specific targeting of cytosine methylation to DNA sequences in vivo

Alexander E. Smith and Kevin G. Ford*

King's College London, Department of Haematological and Molecular Medicine, Guy's, King's and St Thomas' School of Medicine, The Rayne Institute 123 Cold Harbour Lane, London SE5 9NU, UK

*To whom correspondence should be addressed. Tel: +44 207 848 5909; Fax: +44 207 733 3877; Email: kevin.ford{at}kcl.ac.uk

Received July 20, 2006. Revised October 31, 2006. Accepted November 19, 2006.

Development of methods that will allow exogenous imposition of inheritable gene-specific methylation patterns has potential application in both therapeutics and in basic research. An ongoing approach is the use of targeted DNA methyltransferases, which consist of a fusion between gene-targeted zinc-finger proteins and prokaryotic DNA cytosine methyltransferases. These enzymes however have so far demonstrated significant and unacceptable levels of non-targeted methylation. We now report the development of second-generation targeted methyltransferase enzymes comprising enhanced zinc-finger arrays coupled to methyltransferase mutants that are functionally dominated by their zinc-finger component. Both in vitro plasmid methylation studies and a novel bacterial assay reveal a high degree of target-specific methylation by these enzymes. Furthermore, we demonstrate for the first time transient expression of targeted cytosine methyltransferase in mammalian cells resulting in the specific methylation of a chromosomal locus. Importantly, the resultant methylation pattern is inherited through successive cell divisions.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
M. Duca, P. Vekhoff, K. Oussedik, L. Halby, and P. B. Arimondo
The triple helix: 50 years later, the outcome
Nucleic Acids Res., September 1, 2008; 36(16): 5123 - 5138.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. E. Smith, P. J. Hurd, A. J. Bannister, T. Kouzarides, and K. G. Ford
Heritable Gene Repression through the Action of a Directed DNA Methyltransferase at a Chromosomal Locus
J. Biol. Chem., April 11, 2008; 283(15): 9878 - 9885.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.