| AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1 mRNA stability. | |
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MedLine Citation:
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PMID: 17030625 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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DNA methylation is a major determinant of epigenetic inheritance. DNA methyltransferase 1 (DNMT1) is the enzyme responsible for the maintenance of DNA methylation patterns during cell division, and deregulated expression of DNMT1 leads to cellular transformation. We show herein that AU-rich element/poly(U)-binding/degradation factor 1 (AUF1)/heterogeneous nuclear ribonucleoprotein D interacts with an AU-rich conserved element in the 3' untranslated region of the DNMT1 mRNA and targets it for destabilization by the exosome. AUF1 protein levels are regulated by the cell cycle by the proteasome, resulting in cell cycle-specific destabilization of DNMT1 mRNA. AUF1 knock down leads to increased DNMT1 expression and modifications of cell cycle kinetics, increased DNA methyltransferase activity, and genome hypermethylation. Concurrent AUF1 and DNMT1 knock down abolishes this effect, suggesting that the effects of AUF1 knock down on the cell cycle are mediated at least in part by DNMT1. In this study, we demonstrate a link between AUF1, the RNA degradation machinery, and maintenance of the epigenetic integrity of the cell. |
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Authors:
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Jerome Torrisani; Alexander Unterberger; Sachin R Tendulkar; Keisuke Shikimi; Moshe Szyf |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-10-09 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 27 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-14 Completed Date: 2007-01-18 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 395-410 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions Amino Acid Sequence Animals Base Sequence Cell Cycle DNA (Cytosine-5-)-Methyltransferase / metabolism, physiology* DNA Methylation* Epigenesis, Genetic Gene Expression Regulation* Hela Cells Heterogeneous-Nuclear Ribonucleoprotein D / metabolism, physiology* Humans Mice Mice, Inbred BALB C Molecular Sequence Data |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/Heterogeneous-Nuclear Ribonucleoprotein D; 0/hnRNP D0; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1 |
| Comments/Corrections | |
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