Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages

Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR’s transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way. View Full-Text

Keywords: glucocorticoid receptor; inflammation; enhancer RNA; macrophages; tissue specificity; transcription

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MDPI and ACS Style

Greulich, F.; Bielefeld, K.A.; Scheundel, R.; Mechtidou, A.; Strickland, B.; Uhlenhaut, N.H. Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages. Cells 2022, 11, 28. https://doi.org/10.3390/cells11010028

AMA Style

Greulich F, Bielefeld KA, Scheundel R, Mechtidou A, Strickland B, Uhlenhaut NH. Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages. Cells. 2022; 11(1):28. https://doi.org/10.3390/cells11010028

Chicago/Turabian Style

Greulich, Franziska, Kirsten Adele Bielefeld, Ronny Scheundel, Aikaterini Mechtidou, Benjamin Strickland, and Nina Henriette Uhlenhaut. 2022. "Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages" Cells 11, no. 1: 28. https://doi.org/10.3390/cells11010028

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Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages

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