First Author | Gomez JA | Year | 2013 |
Journal | Cell | Volume | 152 |
Issue | 4 | Pages | 743-54 |
PubMed ID | 23415224 | Mgi Jnum | J:193814 |
Mgi Id | MGI:5469744 | Doi | 10.1016/j.cell.2013.01.015 |
Citation | Gomez JA, et al. (2013) The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-gamma Locus. Cell 152(4):743-54 |
abstractText | 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-gamma (IFN-gamma) 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-gamma locus. Thus, this lncRNA regulates epigenetic marking of IFN-gamma-encoding chromatin, expression of IFN-gamma, and susceptibility to a viral and a bacterial pathogen. |