Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes

Bühler, Marc and Mohn, Fabio and Stalder, Lukas and Mühlemann, Oliver. (2005) Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes. Molecular cell, Vol. 18, H. 3. pp. 307-317.

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Official URL: http://edoc.unibas.ch/dok/A5251094

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Cells possess mechanisms to prevent synthesis of potentially deleterious truncated proteins caused by premature translation-termination codons (PTCs). Here, we show that PTCs can induce silencing of transcription of its cognate gene. We demonstrate for immunoglobulin (Ig)-mu minigenes expressed in HeLa cells that this transcriptional silencing is PTC specific and reversible by treatment of the cells with histone deacetylase inhibitors. Furthermore, PTC-containing Ig-mu minigenes are significantly more associated with K9-methylated histone H3 and less associated with acetylated H3 than the PTC-free Ig-mu minigene. This nonsense-mediated transcriptional gene silencing (NMTGS) is also observed with an Ig-gamma minigene, but not with several classic NMD reporter genes, suggesting that NMTGS might be specific for Ig genes. NMTGS represents a nonsense surveillance mechanism by which truncation of a gene's open reading frame (ORF) induces transcriptional silencing through chromatin remodeling. Remarkably, NMTGS is inhibited by overexpression of the putative siRNase 3'hExo, suggesting that siRNA-like molecules are involved in NMTGS.
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Bühler, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:38

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