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- W4313704708 abstract "Abstract The Th2 cytokine interleukin 4 (IL4) promotes macrophage differentiation into alternative subtypes and plays important roles in physiology, in metabolic and inflammatory diseases, in cancer and in tissue regeneration. While the regulatory transcription factor networks governing IL4 signaling are already well-characterized, it is currently less understood which transcriptional coregulators are involved and how they operate mechanistically. In this study, we discover that G protein pathway suppressor 2 (GPS2), a core subunit of the HDAC3 corepressor complex assembled by SMRT and NCOR, represses IL4-dependent enhancer activation in mouse macrophages. Our genome-wide and gene-specific characterization revealed that, instead of directly repressing STAT6, chromatin-bound GPS2 cooperates with SMRT and NCOR to antagonize enhancer activation by lysine demethylase 1A (KDM1A, LSD1). Mechanistically, corepressor depletion increased KDM1A recruitment to enhancers linked to IL4-induced genes, accompanied by demethylation of the repressive histone marks H3K9me2/3 without affecting H3K4me1/2, the classic KDM1A substrates for demethylation in other cellular contexts. This in turn caused enhancer and gene activation already in the absence of IL4/STAT6 and sensitized the STAT6-dependent IL4 responsiveness of macrophages. Thus, our work identified with the antagonistic action of a GPS2-containing corepressor complex and the lysine demethylase KDM1A a hitherto unknown epigenetic corepressor-coactivator switching mechanism that governs alternative macrophage activation." @default.
- W4313704708 created "2023-01-08" @default.
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- W4313704708 creator A5082190458 @default.
- W4313704708 date "2023-01-05" @default.
- W4313704708 modified "2023-10-14" @default.
- W4313704708 title "Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4" @default.
- W4313704708 cites W1531821806 @default.
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- W4313704708 cites W1984061476 @default.
- W4313704708 cites W1991269963 @default.
- W4313704708 cites W2003507204 @default.
- W4313704708 cites W2014677321 @default.
- W4313704708 cites W2015508531 @default.
- W4313704708 cites W2016868307 @default.
- W4313704708 cites W2022884475 @default.
- W4313704708 cites W2035618305 @default.
- W4313704708 cites W2054621094 @default.
- W4313704708 cites W2054835199 @default.
- W4313704708 cites W2065210647 @default.
- W4313704708 cites W2068157186 @default.
- W4313704708 cites W2094221767 @default.
- W4313704708 cites W2115446838 @default.
- W4313704708 cites W2130874539 @default.
- W4313704708 cites W2157771031 @default.
- W4313704708 cites W2162166699 @default.
- W4313704708 cites W2171808845 @default.
- W4313704708 cites W2210414257 @default.
- W4313704708 cites W2266984180 @default.
- W4313704708 cites W2269247182 @default.
- W4313704708 cites W2341539131 @default.
- W4313704708 cites W2414763988 @default.
- W4313704708 cites W2596838981 @default.
- W4313704708 cites W2739174192 @default.
- W4313704708 cites W2741499811 @default.
- W4313704708 cites W2755293472 @default.
- W4313704708 cites W2766367793 @default.
- W4313704708 cites W2776454687 @default.
- W4313704708 cites W2781853139 @default.
- W4313704708 cites W2784315882 @default.
- W4313704708 cites W2786022490 @default.
- W4313704708 cites W2791806364 @default.
- W4313704708 cites W2889397613 @default.
- W4313704708 cites W2896474277 @default.
- W4313704708 cites W2898692674 @default.
- W4313704708 cites W2900569176 @default.
- W4313704708 cites W2901961560 @default.
- W4313704708 cites W2913871604 @default.
- W4313704708 cites W2920852097 @default.
- W4313704708 cites W2938251923 @default.
- W4313704708 cites W2952383643 @default.
- W4313704708 cites W2952664869 @default.
- W4313704708 cites W2954274611 @default.
- W4313704708 cites W2960078024 @default.
- W4313704708 cites W2962172119 @default.
- W4313704708 cites W2963740689 @default.
- W4313704708 cites W2964315448 @default.
- W4313704708 cites W2972909971 @default.
- W4313704708 cites W2977754107 @default.
- W4313704708 cites W3004590664 @default.
- W4313704708 cites W3008324499 @default.
- W4313704708 cites W3011810360 @default.
- W4313704708 cites W3022526195 @default.
- W4313704708 cites W3033653334 @default.
- W4313704708 cites W3045696640 @default.
- W4313704708 cites W3084082246 @default.
- W4313704708 cites W3093209165 @default.
- W4313704708 cites W3111400820 @default.
- W4313704708 cites W3118886003 @default.
- W4313704708 cites W3125946770 @default.
- W4313704708 cites W3134994147 @default.
- W4313704708 cites W3142387341 @default.
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- W4313704708 cites W3165088505 @default.
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- W4313704708 cites W3199421221 @default.
- W4313704708 cites W3209489681 @default.
- W4313704708 cites W3212265769 @default.
- W4313704708 cites W4200397913 @default.
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- W4313704708 doi "https://doi.org/10.1093/nar/gkac1230" @default.
- W4313704708 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36610795" @default.
- W4313704708 hasPublicationYear "2023" @default.
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