[HTML][HTML] The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus

JA Gomez, OL Wapinski, YW Yang, JF Bureau… - Cell, 2013 - cell.com
JA Gomez, OL Wapinski, YW Yang, JF Bureau, S Gopinath, DM Monack, HY Chang
Cell, 2013cell.com
Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific
gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas
Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes
conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses
between SJL/J and B10. S mice and contains several candidate genes, including NeST. The
SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) …
Summary
Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) abundance in activated CD8+ T cells, increased Theiler's virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-γ locus. Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen.
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