Skip Navigation



Nucleic Acids Research Advance Access published online on March 13, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm118
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (492K) Freely available
Right arrow Screen PDF (597K) Freely available
Right arrowOA All Versions of this Article:
35/7/2191    most recent
gkm118v1
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 Espada, J.
Right arrow Articles by Esteller, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Espada, J.
Right arrow Articles by Esteller, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 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

Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells

Jesús Espada1, Esteban Ballestar1, Raffaella Santoro2, Mario F. Fraga1, Ana Villar-Garea1, Attila Németh3, Lidia Lopez-Serra1, Santiago Ropero1, Agustin Aranda4, Helena Orozco4, Vanessa Moreno5, Angeles Juarranz5, Juan Carlos Stockert5, Gernot Längst3, Ingrid Grummt2, Wendy Bickmore6 and Manel Esteller1,*

1Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain, 2Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany, 3Adolf Butenandt Institute, Department of Molecular Biology, Ludwig-Maximilians University, D-8036 Munchen, Germany, 4Department of Biochemistry and Molecular Biology, University of Valencia, E-46100 Burjassot, Valencia, Spain, 5Department of Biology, Faculty of Sciences, Autonomous University of Madrid, 28049 Madrid, Spain and 6MRC Human Genetics Unit, Western General Hospital, EH4 2XU Edinburgh, UK

*To whom correspondence should be addressed. Tel: +34-912246940; Fax: +34-91-22856041; Email: mesteller{at}cnio.es

Received November 22, 2006. Revised February 8, 2007. Accepted February 9, 2007.

The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which are part of the nucleolus. Here we show that human cells lacking DNA methyltransferase 1 (Dnmt1), but not Dnmt33b, have a loss of DNA methylation and an increase in the acetylation level of lysine 16 histone H4 at the rRNA genes. Interestingly, we observed that SirT1, a NAD+-dependent histone deacetylase with a preference for lysine 16 H4, interacts with Dnmt1; and SirT1 recruitment to the rRNA genes is abrogated in Dnmt1 knockout cells. The DNA methylation and chromatin changes at ribosomal DNA observed are associated with a structurally disorganized nucleolus, which is fragmented into small nuclear masses. Prominent nucleolar proteins, such as Fibrillarin and Ki-67, and the rRNA genes are scattered throughout the nucleus in Dnmt1 deficient cells. These findings suggest a role for Dnmt1 as an epigenetic caretaker for the maintenance of nucleolar structure.


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
 Genes Dev.Home page
A. Vaquero and D. Reinberg
Calorie restriction and the exercise of chromatin
Genes & Dev., August 15, 2009; 23(16): 1849 - 1869.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
I. Lopez de Silanes, M. Gorospe, H. Taniguchi, K. Abdelmohsen, S. Srikantan, M. Alaminos, M. Berdasco, R. G. Urdinguio, M. F. Fraga, F. V. Jacinto, et al.
The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
Nucleic Acids Res., May 1, 2009; 37(8): 2658 - 2671.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
M. Esteller
Epigenetics in Cancer
N. Engl. J. Med., March 13, 2008; 358(11): 1148 - 1159.
[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.