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- W3174313367 abstract "Long non-coding RNAs (lncRNAs) are a poorly understood class of regulatory RNAs, known to be highly species specific and capable of binding DNA, RNA, and/or protein to regulate transcriptional and epigenetic networks. Although thousands of lncRNAs have been identified in disease-related screens, only a few have been functionally characterized. Here we identify a primate-specific lncRNA, CHROME, located on human chr2 in a locus associated with premature cardiovascular disease, which regulates the expression of the IL-1 family of cytokines. Using RNA fluorescence in situ hybridization (FISH) and cell fractionation, we show that CHROME is abundant in the nucleus. Furthermore, its expression is induced in primary human macrophages treated with pro-inflammatory Toll-like receptor (TLR) agonists. To investigate CHROME function, we used RNA immunoprecipitation (RIP) to map RNA-protein interactions, and found that CHROME has strong histone binding affinity, suggesting a potential role in gene regulation. Notably, repression of CHROME using anti-sense oligonucleotides leads to a decrease in expression of genes in the IL-1 family gene cluster located nearby on the q arm of chromosome 2, including IL1A , IL1B and IL1RL1 . These data suggest that CHROME may act as a scaffold for chromatin modification of the IL-1 locus, thereby regulating transcription of these potent inflammatory cytokines. This hypothesis is currently being tested using ChIRP (chromatin isolation by RNA purification) coupled with high throughput DNA sequencing and mass spectrometry. As studies support a causal role for IL-1α and IL-1β in the promotion of atherosclerosis, further characterization of CHROME and its regulatory network may uncover novel opportunities for therapeutic intervention in cardiovascular diseases, and other inflammatory diseases in which IL-1 cytokines predominate." @default.
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- W3174313367 date "2016-05-01" @default.
- W3174313367 modified "2023-09-25" @default.
- W3174313367 title "Abstract 594: Long Non-coding RNA Regulation of the Interleukin-1 Gene Family Cluster" @default.
- W3174313367 doi "https://doi.org/10.1161/atvb.36.suppl_1.594" @default.
- W3174313367 hasPublicationYear "2016" @default.
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