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| Status |
Public on Dec 31, 2024 |
| Title |
MOF-mediated PRDX1 acetylation regulates LPS-induced macrophage activation. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophages respond to environmental cues in a plastic manner and play a crucial role in host defense, inflammation, and tissue homeostasis. Macrophage activation undergoes metabolic and transcriptomic reprogramming to adapt and tailor an appropriate response, regulating inflammation. Reactive oxygen species (ROS) have been shown to play a pivotal role in macrophage activation. Nevertheless, the detailed molecular mechanism of how initial redox signals direct macrophage activation is not fully elucidated. Here, we uncover an unconventional role for histone acetyltransferase MOF (also known as KAT8) in regulating LPS-induced macrophage activation via modulating the acetylation of peroxiredoxin 1 (PRDX1), an H2O2 scavenger. We demonstrate that PRDX1 is a novel substrate of MOF and identify the major MOF-mediated acetylation site at lysine 197. K197 acetylation of PRDX1 (K197ac PRDX1) is dynamic and reversely regulated by HDAC6 or SIRT2. We observe that this acetylation is readily diminished in the immediate response to LPS. We demonstrate that K197ac PRDX1 fine-tunes its peroxidase activity, leading to the modulation of intracellular ROS levels in early response to LPS stimulation. Moreover, K197ac PRDX1 specifically regulates ERK1/2 phosphorylation, thereby modulating glycolytic metabolism in inflammatory macrophages. Consequently, K197ac PRDX1 tunes the expression and production of the proinflammatory cytokine, IL-6. Taken together, our findings describe a novel signaling module, MOF-PRDX1-ERK, which regulates LPS-induced macrophage activation at the metabolic and transcriptional levels.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for WT (shCTRL) and MOF depletion (shMOF Knockdown) in mouse bone-marrow derived macrophage.
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| Contributor(s) |
Chen H, Akhtar A |
| Citation missing |
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| |
| Submission date |
May 08, 2023 |
| Last update date |
Dec 31, 2024 |
| Contact name |
Asifa Akhtar |
| E-mail(s) |
akhtarlab_data@ie-freiburg.mpg.de
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| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Chromatin Regulation
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| Lab |
Akhtar Lab
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| Street address |
Stuebeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA970276 |
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