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http://purl.uniprot.org/citations/28011933http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28011933http://www.w3.org/2000/01/rdf-schema#comment"During macrophage activation, expression of IL-1R-associated kinase (IRAK)-M is induced to suppress TLR-mediated responses and is a hallmark of endotoxin tolerance. Endotoxin tolerance requires tight regulation of genes occurring at the transcriptional and epigenetic levels. To identify novel regulators of IRAK-M, we used RAW 264.7 macrophages and performed a targeted RNA interference screen of genes encoding chromatin-modifying enzymes, signaling molecules, and transcription factors involved in macrophage activation. Among these, the transcription factor CCAAT/enhancer binding protein (C/EBP)β, known to be involved in macrophage inactivation, was necessary for the induction of IRAK-M expression. Chromatin immunoprecipitation showed that C/EBPβ was recruited to the IRAK-M promoter following LPS stimulation and was indispensable for IRAK-M transcriptional activation. Among histone 3-modifying enzymes, our screen showed that knockdown of the histone 3 lysine 27 (H3K27) methyltransferase and part of the polycomb recessive complex 2, enhancer of Zeste 2, resulted in IRAK-M overexpression. In contrast, knockdown of the H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat X chromosome suppressed the induction of IRAK-M in response to LPS stimulation. Accordingly, we demonstrated that H3K27 on the IRAK-M promoter is trimethylated in unstimulated cells and that this silencing epigenetic mark is removed upon LPS stimulation. Our data propose a mechanism for IRAK-M transcriptional regulation according to which, in the naive state, polycomb recessive complex 2 repressed the IRAK-M promoter, allowing low levels of expression; following LPS stimulation, the IRAK-M promoter is derepressed, and transcription is induced to allow its expression."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.1600009"xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Kampranis S.C."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Soennichsen B."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Tsatsanis C."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Zacharioudaki V."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Helms M."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Doxaki C."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Patsalos A."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Daskalaki M.G."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Liapis I."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/author"Lyroni K."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/name"J Immunol"xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/pages"1297-1307"xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/title"Epigenetic and Transcriptional Regulation of IRAK-M Expression in Macrophages."xsd:string
http://purl.uniprot.org/citations/28011933http://purl.uniprot.org/core/volume"198"xsd:string
http://purl.uniprot.org/citations/28011933http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28011933
http://purl.uniprot.org/citations/28011933http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28011933
http://purl.uniprot.org/uniprot/#_Q0VB14-mappedCitation-28011933http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28011933
http://purl.uniprot.org/uniprot/#_D6RCU1-mappedCitation-28011933http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28011933
http://purl.uniprot.org/uniprot/#_D3Z007-mappedCitation-28011933http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28011933
http://purl.uniprot.org/uniprot/#_Q8K4B2-mappedCitation-28011933http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28011933
http://purl.uniprot.org/uniprot/D3Z007http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/28011933