The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation
Copyright policy )The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation
Here we found that the transcription repressor DREAM bound to the promoter of the gene encoding A20 to repress expression of this deubiquitinase that suppresses inflammatory NF-κB signaling. DREAM-deficient mice displayed persistent and unchecked A20 expression in response to endotoxin. DREAM functioned by transcriptionally repressing A20 through binding to downstream regulatory elements (DREs). In contrast, binding of the transcription factor USF1 to the DRE-associated E-box domain in the gene encoding A20 activated its expression in response to inflammatory stimuli. Our studies define the critical opposing functions of DREAM and USF1 in inhibiting and inducing A20 expression, respectively, and thereby the strength of NF-κB signaling. Targeting of DREAM to induce USF1-mediated A20 expression is therefore a potential anti-inflammatory strategy for the treatment of diseases associated with unconstrained NF-κB activity, such as acute lung injury.
- UNIVERSITY OF ILLINOIS AT CHICAGO
- University of California San Francisco United States
- University of Illinois at Chicago United States
- University of Illinois United States
- Illinois State University United States
Chromatin Immunoprecipitation, Ubiquitin-Protein Ligases, Acute Lung Injury, Immunoblotting, Real-Time Polymerase Chain Reaction, Mice, Animals, Tumor Necrosis Factor alpha-Induced Protein 3, Inflammation, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, NF-kappa B, Kv Channel-Interacting Proteins, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, Cysteine Endopeptidases, Disease Models, Animal, Gene Expression Regulation
Chromatin Immunoprecipitation, Ubiquitin-Protein Ligases, Acute Lung Injury, Immunoblotting, Real-Time Polymerase Chain Reaction, Mice, Animals, Tumor Necrosis Factor alpha-Induced Protein 3, Inflammation, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, NF-kappa B, Kv Channel-Interacting Proteins, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, Cysteine Endopeptidases, Disease Models, Animal, Gene Expression Regulation
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