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 Curradi, M.
Right arrow Articles by Landsberger, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Curradi, M.
Right arrow Articles by Landsberger, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2002, p. 3157-3173, Vol. 22, No. 9
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.9.3157-3173.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Molecular Mechanisms of Gene Silencing Mediated by DNA Methylation

Michela Curradi, Annalisa Izzo, Gianfranco Badaracco, and Nicoletta Landsberger*

Dipartimento di Biologia Strutturale e Funzionale, Università degli Studi dell'Insubria, 21052 Busto Arsizio (Va), Italy

Received 27 December 2001/ Accepted 29 January 2002

DNA methylation and chromatin modification operate along a common pathway to repress transcription; accordingly, several experiments demonstrate that the effects of DNA methylation can spread in cis and do not require promoter modification. In order to investigate the molecular details of the inhibitory effect of methylation, we microinjected into Xenopus oocytes a series of constructs containing a human CpG-rich sequence which has been differentially methylated and cloned at different positions relative to a specific promoter. The parameters influencing the diffusion of gene silencing and the importance of histone deacetylation in the spreading effect were analyzed. We demonstrate that a few methylated cytosines can inhibit a flanking promoter but a threshold of modified sites is required to organize a stable, diffusible chromatin structure. Histone deacetylation is the main cause of gene repression only when methylation does not reach levels sufficient to establish this particular structure. Moreover, contrary to the common thought, promoter modification does not lead to the greater repressive effect; the existence of a competition between transactivators and methyl-binding proteins for the establishment of an open conformation justifies the results obtained.

* Corresponding author. Mailing address: Dipartimento di Biologia Strutturale e Funzionale, Università degli Studi dell'Insubria, Via Alberto Da Giussano 12, 21052 Busto Arsizio (Va), Italy. Phone: 390331339406. Fax: 390331339459. E-mail: landsben{at}uninsubria.it.

Molecular and Cellular Biology, May 2002, p. 3157-3173, Vol. 22, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.9.3157-3173.2002
Copyright © 2002, 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 © 2002 by the American Society for Microbiology. All rights reserved.