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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 11:28 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 GRmediated 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Enhancer Rna ; Glucocorticoid Receptor ; Inflammation ; Macrophages ; Tissue Specificity ; Transcription; Receptor-binding; Chromatin Accessibility; Histone Modifications; Gene-expression; Dna-binding; R Package; Transcription; Gr; Sequence; Recruitment
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 28 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Institute(s) Institute of Diabetes and Cancer (IDC)
Grants Deutsche Forschungsgemeinschaf
European Research Council
Deutsche Forschungsgemeinschaft