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Identifier |
000382519 |
Title |
Epigenetic regulation of IRAK-M and macrophage activation /inactivation |
Alternative Title |
Επιγενετική ρύθμιση του IRAK-M και πως αυτο επηρεάζει την ενεργοποίηση /απενεργοποίηση των μακροφάγων |
Author
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Πάτσαλος, Ανδρέας
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Thesis advisor
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Τσατσάνης, Χρήστος
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Reviewer
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Καμπράνης, Σωτήριος
Καρδάσης, Δημήτριος
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Abstract |
Proper regulation of chromatin structure is necessary for the maintenance of cell type-specific gene expression patterns. Diverse macrophage expression patterns control their polarization and activation/inactivation status. During macrophage activation, interleukin-1 receptor-associated kinase (IRAK)-M acts as a functional decoy preventing uncontrolled toll-like receptor / interleukin-1-mediated responses. Despite its important role, the transcriptional and epigenetic regulation of IRAK-M expression is not fully understood. Our study investigates the role of chromatin regulators and transcription factors in controlling IRAK-M expression upon activation of macrophages by gram (-) bacterial lipopolysaccharide (LPS). Here, we present an RNAi screen in mouse RAW264.7 macrophages of over 60 genes encoding chromatin proteins and transcription factors. We identified 6 proteins that exhibit diverse phenotypes and activation potential upon knockdown following LPS treatment. We focused on two chromatin regulators EZH2 (Histone-lysine N-methyltransferase) and UTX (Ubiquitously transcribed tetratricopeptide repeat, X chromosome) with antagonizing actions. We propose that they are localized on the promoter of IRAK-M to mediate histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, we found that the transcription factor CEBPb directly binds on the promoter of IRAK-M regulating its transcription. Depletion of CEBPb reduced both protein and mRNA IRAK-M expression. These data indicate that EZH2, UTX and CEBPb are key regulators of IRAK-M expression in macrophages activated through TLR4.
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Language |
English |
Subject |
Epigenetics |
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IRAK-M |
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Macrophages |
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Επιγενετική |
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Μακροφάγα |
Issue date |
2013-07-16 |
Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/6/6/c/metadata-dlib-1391774379-421669-20550.tkl
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Views |
170 |