MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Jørgensen, H. F.
Right arrow Articles by Bird, A. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jørgensen, H. F.
Right arrow Articles by Bird, A. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2004, p. 3387-3395, Vol. 24, No. 8
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.8.3387-3395.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mbd1 Is Recruited to both Methylated and Nonmethylated CpGs via Distinct DNA Binding Domains

Helle F. Jørgensen,1 Ittai Ben-Porath,2,{dagger} and Adrian P. Bird1*

The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom,1 Department of Cellular Biochemistry, Hebrew University Medical School, Jerusalem, Israel2

Received 17 November 2003/ Returned for modification 15 December 2003/ Accepted 22 January 2004

MBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences. Like other MBD proteins, MBD1 localizes to nuclear foci that in mice are rich in methyl-CpG. In methyl-CpG-deficient mouse cells, however, Mbd1 remains localized to heterochromatic foci whereas other MBD proteins become dispersed in the nucleus. We find that Mbd1a, a major mouse isoform, contains a CXXC domain (CXXC-3) that binds specifically to nonmethylated CpG, suggesting an explanation for methylation-independent localization. Transfection studies demonstrate that the CXXC-3 domain indeed targets nonmethylated CpG sites in vivo. Repression of nonmethylated reporter genes depends on the CXXC-3 domain, whereas repression of methylated reporters requires the MBD. Our findings indicate that MBD1 can interpret the CpG dinucleotide as a repressive signal in vivo regardless of its methylation status.

* Corresponding author. Mailing address: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Mayfield Rd., Edinburgh EH9 3JR, United Kingdom. Phone: 44 131 650 8695. Fax: 44 131 650 5379. E-mail: A.Bird{at}ed.ac.uk.

{dagger} Present address: The Whitehead Institute for Biomedical Research, Cambridge, Mass.

Molecular and Cellular Biology, April 2004, p. 3387-3395, Vol. 24, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.8.3387-3395.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2004 by the American Society for Microbiology. All rights reserved.