C-terminal binding protein 2 interacts with JUNB to control macrophage inflammation.
Life Sci. All. 8:16 (2025)
Although acute inflammatory responses are critical for survival, chronic inflammation is a leading cause of disease and mortality worldwide. Nevertheless, our mechanistic understanding of pathogenesis is still limited and precise treatment options are lacking. Here, we investigate the role of the transcriptional co-repressors C-terminal binding protein (CTBP) 1 and 2 in murine and human macrophage activation using loss-of-function models to show that CTBP2 but not CTBP1 controls inflammatory gene expression. We find that CTBP2 occupies cis-regulatory elements of inflammatory genes together with the transcription factors NF-κB and AP-1 and forms a co-repressor complex. Rescue of Ctbp1/2 double knockout cells with WT, oligomeric CTBP2 attenuates inflammatory responses, whereas a monomeric mutant does not. Differential profiling of CTBP2's WT and monomeric interactome confirms oligomer-specific interactions with multiple repressors. Conversely, monomers retain the ability to interact with AP-1 and RNA polymerase II, boosting gene expression. Our findings point to an important function for CTBP2 in fine-tuning inflammatory gene expression, potentially unveiling novel therapeutic targets for the treatment of inflammatory diseases.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Proinflammatory Cytokines; Ctbp; Lsd1; Activation; Mechanisms; Inhibition; Repressor; Package; Hdac1
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Language
english
Publication Year
2025
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0
HGF-reported in Year
2025
ISSN (print) / ISBN
2575-1077
e-ISSN
2575-1077
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Volume: 8,
Issue: 8,
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Article Number: 16
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EMBO Press
Publishing Place
Heidelberg
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Peer reviewed
Institute(s)
Institute of Diabetes and Endocrinology (IDE)
POF-Topic(s)
30202 - Environmental Health
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PSP Element(s)
G-501900-259
Grants
International Helmholtz-Edinburgh Research School for Epigenetics
TUM Global Incentive Funds
DFG
German Research Foundation DFG
Novo Nordisk Foundation (NNF)
Next Generation Sequencing Competence Network (NGS-CN)
DFG Research Infrastructure Program
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Erfassungsdatum
2025-06-26