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Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injury-induced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition.
Pubmed ID: 30484118 RIS Download
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Suite of motif-based sequence analysis tools to discover motifs using MEME, DREME (DNA only) or GLAM2 on groups of related DNA or protein sequences; search sequence databases with motifs using MAST, FIMO, MCAST or GLAM2SCAN; compare a motif to all motifs in a database of motifs; associate motifs with Gene Ontology terms via their putative target genes, and analyze motif enrichment using SpaMo or CentriMo. Source code, binaries and a web server are freely available for noncommercial use.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsDrosophila melanogaster with name flfl[N42]/TM6B, Tb[1] from BDSC.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Iba1/AIF1
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets IkappaB-alpha, phospho (Ser32 / Ser36)
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis monoclonal targets LYVE1
View all literature mentionsThis polyclonal targets IRF8
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsThis polyclonal targets GFP-1010
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis monoclonal targets Sfpi1
View all literature mentionsMus musculus with name B6.Cg-Spi1tm2Dgt/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6.129X1-Sarm1tm1Aidi/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Irf8tm1.1Hm/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Aldh1l1-EGFP)OFC789Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.129(Cg)-Ccr2tm2.1Ifc/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Irf8tm1.1Hm/J from IMSR.
View all literature mentionsThis monoclonal targets IkappaB-alpha, phospho (Ser32 / Ser36)
View all literature mentionsMus musculus with name B6.129(Cg)-Ccr2tm2.1Ifc/J from IMSR.
View all literature mentionsMus musculus with name B6.129X1-Sarm1tm1Aidi/J from IMSR.
View all literature mentionsThis monoclonal targets Iba1/AIF1
View all literature mentionsThis monoclonal targets LYVE1
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Spi1tm2Dgt/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Aldh1l1-EGFP)OFC789Gsat/Mmucd from MMRRC.
View all literature mentionsThis polyclonal targets GFP-1010
View all literature mentionsMus musculus with name B6.129(Cg)-Ccr2tm2.1Ifc/J from IMSR.
View all literature mentionsThis polyclonal targets IRF8
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsMus musculus with name B6.Cg-Irf8tm1.1Hm/J from IMSR.
View all literature mentionsThis monoclonal targets IkappaB-alpha, phospho (Ser32 / Ser36)
View all literature mentionsThis monoclonal targets Sfpi1
View all literature mentionsThis polyclonal targets IRF8
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis monoclonal targets Iba1/AIF1
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis polyclonal targets GFP-1010
View all literature mentionsThis monoclonal targets LYVE1
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsMus musculus with name B6.Cg-Spi1tm2Dgt/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Aldh1l1-EGFP)OFC789Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.129X1-Sarm1tm1Aidi/J from IMSR.
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