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How to tame your genes: Mechanisms of inflammatory gene repression by glucocorticoids.
FEBS Lett. 596, 2596-2616 (2022)
Glucocorticoids (GCs) are widely used therapeutic agents to treat a broad range of inflammatory conditions. Their functional effects are elicited by binding to the glucocorticoid receptor (GR), which regulates transcription of distinct gene networks in response to ligand. However, the mechanisms governing various aspects of undesired side effects versus beneficial immunomodulation upon GR activation remain complex and incompletely understood. In this review, we discuss emerging models of inflammatory gene regulation by GR, highlighting GR's regulatory specificity conferred by context-dependent changes in chromatin architecture and transcription factor or co-regulator dynamics. GR controls both gene activation and repression, with the repression mechanism being central to favourable clinical outcomes. We describe current knowledge about 3D genome organisation and its role in spatiotemporal transcriptional control by GR. Looking beyond, we summarise the evidence for dynamics in gene regulation by GR through cooperative convergence of epigenetic modifications, transcription factor crosstalk, molecular condensate formation and chromatin looping. Further characterising these genomic events will reframe our understanding of mechanisms of transcriptional repression by GR.
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Publication type
Article: Journal article
Document type
Review
Keywords
Chromatin ; Epigenetic ; Gene Repression ; Glucocorticoid ; Glucocorticoid Receptor ; Inflammation ; Macrophage ; Phase Condensates ; Transcription
ISSN (print) / ISBN
0014-5793
e-ISSN
1873-3468
Journal
FEBS Letters
Quellenangaben
Volume: 596,
Issue: 20,
Pages: 2596-2616
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
Else Kroner-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft
Deutsche Forschungsgemeinschaft