The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-γ Locus

Gómez, Jessica; Wapinski, Orly L.; Yang, Yul W.; Bureau, Jean‐François; Gopinath, Smita; Monack, Denise M.; Chang, Howard Y.; Brahic, Michel; Kirkegaard, Karla

doi:10.1016/j.cell.2013.01.015

Cited by 597 publications

(592 citation statements)

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“…Activating HMTs, such as the tri thorax family member mixed-lineage leukaemia (MLL; also known as KMT2A), which adds methyl groups to histone H3 lysine 4 (H3K4), is especially important for the retention of cytokine production specifically in memory T H 2 cells, but not T H 1 cells 142 . The recruitment of chromatinmodifying complexes to specific DNA loci is also promoted by long non-coding RNAs (lncRNAs), such as with Tmevpg1 (also known as NeSt) recruitment of MLL to the Ifng locus 143,144 , which bind through base pair complementarity and direct chromatin modifiers to specific sites in the genome 145 (FIG. 5c).…”

Section: Dna Accessibility By Modification Of Dna and Histonesmentioning

confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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| CD4 + T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4 + T cell plasticity by examining the molecular mechanisms that regulate it -from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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Section: Dna Accessibility By Modification Of Dna and Histonesmentioning

confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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“…(Albrecht et al, 2010(Albrecht et al, , 2011Chabelskaya et al, 2014;Chao et al, 2012;Gong et al, 2011;Grieshaber et al, 2006;Mann et al, 2012;Moon et al, 2013;Ortega et al, 2012;PadalonBrauch et al, 2008;Pfeiffer et al, 2007) crRNA, (Bhaya et al, 2011;Heidrich and Vogel, 2013;Sampson et al, 2013;van der Oost et al, 2014) (Georg and Hess, 2011;Giangrossi et al, 2010;GonzaloAsensio et al, 2013;Gottesman and Storz, 2011;Lasa et al, 2011;Lee and Groisman, 2010;Padalon-Brauch et al, 2008;Sesto et al, 2013) circRNAs rare varies arise from the 3'-5' ligation of both ends of linear RNA molecules n. a. -- (Doose et al, 2013;Vicens and Cech, 2009) - (Conway et al, 2014;Weinberg et al, 2009) Carpenter et al, 2013;Gomez et al, 2013;Iiott et al, 2014;Imamura et al, 2014;Li et al, 2014;Rapicavoli et al, 2013) poly ( (Jeck and Sharpless, 2014;Memczak et al, 2013) 1 : in the given context of bacterial infection of eukaryo...…”

Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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“…Modulated expression of lncRNAs under LPS-induced stress has been identified in human monocytes, and these molecules are therefore considered to be essential regulators of the innate immune response (Ilott et al 2014). Moreover, the lncRNA NeST [nettoie Salmonella pas Theiler's (cleanup Salmonella not Theiler's)] was reported to control the IFN-γ locus in CD8 + T cells and thus decrease the vulnerability to Salmonella infection in mice after LPS treatment (Gomez et al 2013). Do lncRNAs also mediate stress-induced ATI?…”

Section: Do Lncrnas Mediate Ati?mentioning

confidence: 99%