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MacrophageEGR SIGNED
Egr1 and Egr2 regulate opposite transcriptional programs in macrophages
Total Cost €
0EC-Contrib. €
0Partnership
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0MacrophageEGR project word cloud
Explore the words cloud of the MacrophageEGR project. It provides you a very rough idea of what is the project "MacrophageEGR" about.
outputs
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represses
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mouse
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Project "MacrophageEGR" data sheet
The following table provides information about the project.
| Coordinator |
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Total cost | 175˙572 € |
| EC max contribution | 175˙572 € (100%) |
| Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
| Code Call | H2020-MSCA-IF-2019 |
| Funding Scheme | MSCA-IF-EF-RI |
| Starting year | 2021 |
| Duration (year-month-day) | from 2021-03-09 to 2023-03-08 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM | NL (AMSTERDAM) | coordinator | 175˙572.00 |
Map
Project objective
Macrophages play important roles in many aspects of immunity and therefore contribute to a diverse range of human inflammatory diseases, including atherosclerosis. The expression of macrophage genes is tightly controlled by regulatory DNA elements, such as enhancers. When macrophages are exposed to external stimuli, specific transcription factors affect enhancer activity, thereby impacting macrophage function in health and disease. I am investigating macrophage enhancer activation by interleukin-4 (IL-4). IL-4 is an important anti-inflammatory cytokine that suppresses macrophage activation and regulates immune responses during parasitic infections and allergies. I discovered that IL-4 activates the transcription factor Egr2 leading to specific IL-4-induced enhancer activation in macrophages. I surprisingly noticed that Egr1, while binding highly similar DNA motifs as Egr2, actually represses enhancer activity when macrophages are exposed to pro-inflammatory stimuli, indicating antagonistic effects of Egr1 and Egr2. By targeting transcriptional regulators, macrophages can be skewed to disease-favorable phenotypes. I here propose to investigate and target Egr1 and Egr2 in pro- and anti-inflammatory macrophage phenotypes in vitro and in disease. Aim 1: To elucidate the molecular mechanism resulting in differential outputs of Egr1 and Egr2 binding, I will study the transcription factor complexes in which Egr1/Egr2 function. Aim 2: To characterize the function of Egr1 and Egr2 in macrophages, I will study the effects of Egr1/Egr2 deletion in mouse and human macrophages. Aim 3: To study the roles of Egr1 and Egr2 in macrophage-driven diseases, I will delete Egr1/Egr2 in macrophages and assess the effect of deletion on atherosclerosis and endotoxemia. My proposed studies will reveal the role of macrophage Egr1 and Egr2 in disease and contribute to increased knowledge on how disease-associated signals regulate enhancer activity in disease-relevant cell types.
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The information about "MACROPHAGEEGR" are provided by the European Opendata Portal: CORDIS opendata.
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