Research article summary (published 26 Aug 2009):

Loss of human ribosomal gene CpG methylation enhances cryptic RNA polymerase II transcription and disrupts ribosomal RNA processing.

Full Abstract

Epigenetic methyl-CpG silencing of the ribosomal RNA (rRNA) genes is thought to downregulate rRNA synthesis in mammals. In contrast, we now show that CpG methylation in fact positively influences rRNA synthesis and processing. Human HCT116 cells, inactivated for DNMT1 and DNMT3b or treated with aza-dC, lack CpG methylation and reactivate a large fraction of normally silent rRNA genes. Unexpectedly, these cells display reduced rRNA synthesis and processing and accumulate unprocessed 45S rRNA. Reactivation of the rRNA genes is associated with their cryptic transcription by RNA polymerase II. Ectopic expression of cryptic rRNA gene transcripts recapitulates the defects associated with loss of CpG methylation. The data demonstrate that rRNA gene silencing prevents cryptic RNA polymerase II transcription of these genes. Lack of silencing leads to the partial disruption of rRNA synthesis and rRNA processing, providing an explanation for the cytotoxic effects of loss of CpG methylation.

Author information

Author/s: Gagnon-Kugler, Thérèse (T); Langlois, Frédéric (F); Stefanovsky, Victor (V); Lessard, Frédéric (F); Moss, Tom (T);

Affiliation: Cancer Research Centre, CHUQ-HDQ Research Centre, Pavillon St. Patrick, 9 Rue McMahon, Québec, QC G1R 3S3, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Molecular cell (Mol Cell), published in United States. (Language: eng)

Reference: 2009-Aug; vol 35 (issue 4) : pp 414-25

Dates: Created 2009/08/31; Completed 2009/09/10;

PMID: 19716787, status: MEDLINE (last retrieval date: 9/10/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Azacitidine - analogs & derivatives; pharmacology Cell Nucleolus - drug effects; metabolism; pathology Cell Proliferation Cell Survival CpG Islands DNA (Cytosine-5-)-Methyltransferase - antagonists & inhibitors; genetics; metabolism DNA Methylation - drug effects DNA, Ribosomal - metabolism Enzyme Inhibitors - pharmacology

Enzyme Inhibitors - pharmacology HCT116 Cells Humans Kinetics RNA Polymerase II - genetics; metabolism RNA Processing, Post-Transcriptional RNA Stability RNA, Ribosomal - metabolism Transcription, Genetic - drug effects

Associated Chemicals: DNA, Ribosomal (0) ; Enzyme Inhibitors (0) ; RNA, Ribosomal (0) ; RNA, ribosomal, 45S (0) ; decitabine (2353-33-5) ; Azacitidine (320-67-2) ; DNA methyltransferase 3B (EC 2.1.1.-) ; DNA (Cytosine-5-)-Methyltransferase (EC 2.1.1.37) ; DNA (cytosine-5-)-methyltransferase 1 (EC 2.1.1.37) ; RNA Polymerase II (EC 2.7.7.-)

Related articles

These are the highest related articles currently in the database:

• Specific inhibition of DNMT1 by antisense oligonucleotides induces re-expression of estrogen receptor-alpha (ER) in ER-negative human breast cancer cell lines. 30 Aug 2003
• Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. 30 Dec 2001
• Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter. 8 Mar 2008
• Decitabine (5-Aza-2'-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells. 30 Oct 2000
• Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1 gene in fragile X cells treated with 5-azadeoxycytidine. 13 Jul 2002
• Reactivation of silenced genes and transcriptional therapy. 30 Dec 2002
• Eliminating epigenetic barriers induces transient hormone-regulated gene expression in estrogen receptor negative breast cancer cells. Mar 2008
• RAS-mediated epigenetic inactivation of OPCML in oncogenic transformation of human ovarian surface epithelial cells. 27 Dec 2005
• Differentially methylated alleles in a distinct region of the human interleukin-1alpha promoter are associated with allele-specific expression of IL-1alpha in CD4+ T cells. 18 Jun 2006
• Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. 29 Sep 2001

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.