Cataloguing novel intergenic RNA expression from GR-bound macrophage enhancers

Inflammation is a complex biological reaction to infection, tissue damage and injury. In its acute form, inflammation is an innate response of the body to eliminate pathogens and to initiate healing. However, if inflammation is not resolved, it progresses towards a chronic state, contributing to pathologies such as rheumatoid arthritis, pulmonary disease or metabolic syndrome. One of the most prominent anti-inflammatory drug targets is the glucocorticoid receptor (GR). GR belongs to the nuclear hormone receptor family of ligand-activated transcription factors. Its ligands cortisone, dexamethasone (Dex) and prednisolone are widely prescribed immune suppressants. Unfortunately, chronic treatment regimens are accompanied by severe side effects including diabetes, osteoporosis and hypertension, and ultimately limit their use. We performed nascent transcriptome analysis in bone marrow-derived macrophages treated with the inflammatory TLR4 ligand LPS, or LPS and Dexamethasone. We aimed to identify novel intergenic RNAs that might contribute to the anti-inflammatory response downstream of GR occupancy. Here, we report the identification of 1,926 intergenic RNAs expressed from GR-bound enhancers. Their expression strongly correlates with enhancer marks like H3K4me1, H3K27ac and DnaseI-hypersensitivity. We are currently analysing H3K4me1/2/3, H3K27ac, RNA polymerase 2 and DnaseI-hypersensitivity NGS data of macrophages treated with LPS or LPS and Dexamethasone. We want to pinpoint the role of intergenic RNA expression, enhancer activation status and expression of their putative target genes to understand the functional role of novel non coding cis-regulatory RNAs.      «

Inflammation is a complex biological reaction to infection, tissue damage and injury. In its acute form, inflammation is an innate response of the body to eliminate pathogens and to initiate healing. However, if inflammation is not resolved, it progresses towards a chronic state, contributing to pathologies such as rheumatoid arthritis, pulmonary disease or metabolic syndrome. One of the most prominent anti-inflammatory drug targets is the glucocorticoid receptor (GR). GR belongs to the nuclea...     »