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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 Πάτσαλος, Ανδρέας
Thesis advisor Τσατσάνης, Χρήστος
Reviewer Καμπράνης, Σωτήριος
Καρδάσης, Δημήτριος
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.
Language English
Subject Epigenetics
IRAK-M
Macrophages
Επιγενετική
Μακροφάγα
Issue date 2013-07-16
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/6/6/c/metadata-dlib-1391774379-421669-20550.tkl Bookmark and Share
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