RNA-mediated gene activation

Jiao, Alan; Slack, Frank J.

doi:10.4161/epi.26942

Cited by 67 publications

(50 citation statements)

References 91 publications

(194 reference statements)

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“…Since enhancer RNA (eRNA) production is associated with functional enhancer elements (Jiao and Slack, 2013), we next investigated whether hHS-8 eRNA was transcribed during IFN-γ priming and LPS stimulation of THP-1 cells and primary human MDMs. In both cell types, similar to our findings with TNF gene transcription initiated at the promoter, IFN-γ as a single stimulus did not induce transcription of hHS-8 eRNA (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

2014

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SUMMARY IFN-γ priming sensitizes monocytes/macrophages to lipopolysaccharide (LPS) stimulation, resulting in augmented expression of a set of genes including TNF. Here, we demonstrate that IFN-γ priming of LPS-stimulated TNF transcription requires a distal TNF/LT locus element 8 kb upstream of the TNF transcription start site (hHS-8). IFN-γ stimulation leads to increased DNase I accessibility of hHS-8 and its recruitment of IRF1, and subsequent LPS stimulation enhances H3K27 acetylation and induces enhancer RNA synthesis at hHS-8. Ablation of IRF1 or targeting the hHS-8 IRF1 binding site in vivo with Cas9 linked to the KRAB repressive domain abolishes IFN-γ priming while LPS induction of the gene is unaffected. Thus, IFN-γ poises a distal enhancer in the TNF/LT locus by chromatin remodeling and IRF1 recruitment, which then drives enhanced TNF gene expression in response to a secondary TLR stimulus.

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Section: Resultsmentioning

confidence: 99%

A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

2014

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“…Since then, several studies have illustrated the ability of dsRNA, shRNA, or miR to induce promoter activity of numerous genes both in vitro and in vivo (26). However, only a few reports place it in a physiological context (2), which explains why RNAa is often perceived as an artificial "test-tube" process or only as a tool to specifically affect in vivo gene expression.…”

Section: Discussionmentioning

confidence: 99%

RNA Activation of the Vascular Endothelial Growth Factor Gene (VEGF) Promoter by Double-Stranded RNA and Hypoxia: Role of Noncoding VEGF Promoter Transcripts

Lopez

Wagner

Hofman

et al. 2016

Molecular and Cellular Biology

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f RNA activation (RNAa) is a gene regulation process in which promoter-targeted short double-stranded RNAs (dsRNAs) or microRNAs (miRs) induce target gene expression at the transcriptional level. Here, we investigate the presence of cryptic promoter transcripts within the VEGF promoter. Single-strand sense and antisense noncoding vascular endothelial growth factor (NcVEGF) promoter transcripts are identified, and their respective expression is studied in cells transfected with a VEGF promoter targeted dsRNA, namely, dsVEGF706, in hypoxic cells and in human malignant lung tissues. Interestingly, in dsVEGF706-transfected, as well as in hypoxic cells, NcVEGF expression levels increase coordinately with coding VEGF expression. Ago2 interaction with both sense and antisense NcVEGFs is increased in hypoxic cells, whereas in dsVEGF706-transfected cells, Ago2 and the antisense strand of the dsRNA interact specifically with the sense NcVEGF transcript. Furthermore, both dsVEGF706 and ectopic NcVEGF transcripts are able to activate the VEGF promoter endogenously present or in a reporter construct. Finally, using small interfering RNA targeting Ago2, we show that RNAa plays a role in the maintenance of increased VEGF and NcVEGF expression after hypoxia. Given the central role of VEGF in major human diseases, including cancer, this novel molecular mechanism is poised to reveal promising possibilities for therapeutic interventions.

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“…Historically, the research community has debated how to exactly define epigenetics (Deans and Maggert, 2015). Depending on the perspective of the investigator, a range of potential mechanisms are recognized, including covalent modifications of histones (Bannister and Kouzarides, 2011), DNA methylation (Bird, 2002), and gene regulation by a variety of non-coding RNAs (Jiao and Slack, 2014). Some biomedical research venues exemplify this broader definition of epigenetic mechanisms, and include both heritable and with-in generation processes (e.g., the U.S. National Institute of Health's Roadmap Epigenetics projecthttp://www.roadmapepigenomics.org/overview).…”

Section: Epigenetics-a Brief Overviewmentioning

confidence: 99%

Ecological Epigenetics in Marine Metazoans

Hofmann

2017

Front. Mar. Sci.

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In this horizon scan article, I review the emerging area of ecological epigenetics in marine animals with studies of DNA methylation as the primary focus. Epigenetic mechanisms such as DNA methylation have the capacity to create rapid changes in phenotypic plasticity. Epigenetic modifications of DNA are mechanisms that modify gene expression, and may do so in marine animals in an environmentally-induced manner. Thus, changes in the transcriptome that are driven by DNA methylation in response to environmental change may be one process by which marine animals can respond to anthropogenic, environmental change. From a technical standpoint, assays to quantify levels of DNA methylation, and next-generation sequencing approaches are opening up new avenues of exploration, such as simultaneously profiling the transcriptome and the methylome. A horizon scan for this topic suggests that the use of epigenomics and other methods to quantify DNA methylation will likely reveal important mechanisms of response to rapid environmental change in marine metazoans.

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RNA-mediated gene activation

Cited by 67 publications

References 91 publications

A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

RNA Activation of the Vascular Endothelial Growth Factor Gene (VEGF) Promoter by Double-Stranded RNA and Hypoxia: Role of Noncoding VEGF Promoter Transcripts

Ecological Epigenetics in Marine Metazoans

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