Abstract
Recent studies have indicated that non-coding RNAs transcribed from enhancer regions are important regulators of enhancer function and gene expression. In this report, we have characterised the expression of six enhancer RNAs (eRNAs) induced in human monocytic THP1 cells following activation of the innate immune response by lipopolysaccharide (LPS). Specifically, we have demonstrated that LPS-induced expression of individual eRNAs is mediated through divergent intracellular signalling pathways that includes NF-κB and the mitogen activated protein kinases, extracellular regulated kinase-1/2 and p38.
Highlights
Cells of the innate immune response, including circulating monocytes, prevent infection through the rapid removal of invading pathogens [1]
It is becoming apparent that the action of these enhancers is dependent upon the production of enhancer RNAs (eRNAs), an observation supported by the FANTOM project that identified 43 000 bi-directionally transcribed eRNAs across a diverse range of human tissues [16]
Dynamic activation and repression of enhancers has been shown to occur upon exposure of immune cells to inflammatory stimuli, suggesting that enhancers have a key role in regulating inflammatory gene expression [13,14,24]
Summary
Cells of the innate immune response, including circulating monocytes, prevent infection through the rapid removal of invading pathogens [1]. LPS stimulation has been shown to stimulate multiple mitogen activated protein kinase (MAPK) signalling pathways including extracellular signal-regulated kinases (ERK1/2), cJun N-terminal kinases (JNK1/2) and p38 MAPK [2]. This results in the activation of additional transcription factors involved in the antimicrobial response including activator protein (AP-1) and cAMP-responsive-element-binding protein 1 (CREB1) [3]. Recent studies have indicated that the action of enhancers is dependent upon the transcription of non-coding RNAs, entitled enhancer RNAs (eRNAs) [7] These are involved both in the establishment of enhancer sites and in the subsequent looping and regulation of gene expression in cis [8,9,10,11,12,13]. Since little is known about the signalling pathways that regulate the production of these immune-related eRNAs, we have examined the role of NF-jB and the MAPK intracellular pathways and shown that the expression of eRNAs is regulated by multiple divergent mechanisms
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