title: The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus.
abstract: 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.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: J Antonio
authors: JA
authors: Gomez
authors: Orly L
authors: OL
authors: Wapinski
authors: Yul W
authors: YW
authors: Yang
authors: Jean-François
authors: JF
authors: Bureau
authors: Smita
authors: S
authors: Gopinath
authors: Denise M
authors: DM
authors: Monack
authors: Howard Y
authors: HY
authors: Chang
authors: Michel
authors: M
authors: Brahic
authors: Karla
authors: K
authors: Kirkegaard
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D062085:RNA, Long Noncoding / Q000235:genetics*; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D017945:Theilovirus / Q000276:immunology
chemical_list: D062085:RNA, Long Noncoding; D007371:Interferon-gamma