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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247945 | GEO | 2023/12/21

REPOSITORIES: GEO

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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ATAC]

Project description:To investigate the enhancer/promoter activity in TLR4-regulated inflammatory genes, we used bone marrow-derived macrophages treated with or without KLA. We then analyzed open chromatin regions obtained from ATAC-seq data.

2023-12-21 | GSE247937 | GEO

A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [RNA-seq]

Project description:To investigate the cooperative function NCoR/HDAC3/PGC1β complex in TLR4-regulated inflammatory genes, we used bone marrow-derived macrophages treated with or without KLA. We then performed gene expression profiling analysis using data obtained from RNA-seq.

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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ChIP-seq]

Project description:To investigate the genomic localization of NCoR/HDAC3/PGC1β complex and the enhancer/promoter activity in inflammatory genes, we used NCoR KO or PGC1β KO bone marrow-derived macrophages and Traf6 siRNA knockdown bone marrow-derived macrophages. We then performed chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K27ac, NCoR, HDAC3, PGC1β, ERK1, p65, Fosl2, PU.1 and p300.

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A TLR4/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation.

Project description:The nuclear receptor corepressor (NCoR) forms a complex with histone deacetylase 3 (HDAC3) that mediates repressive functions of unliganded nuclear receptors and other transcriptional repressors by deacetylation of histone substrates. Recent studies provide evidence that NCoR/HDAC3 complexes can also exert coactivator functions in brown adipocytes by deacetylating and activating PPARγ coactivator 1α (PGC1α) and that signaling via receptor activator of nuclear factor kappa-B (RANK) promotes the formation of a stable NCoR/HDAC3/PGC1β complex that coactivates nuclear factor kappa-B (NFκB)- and activator protein 1 (AP-1)-dependent genes required for osteoclast differentiation. Here, we demonstrate that activation of Toll-like receptor (TLR) 4, but not TLR3, the interleukin 4 (IL4) receptor nor the Type I interferon receptor, also promotes assembly of an NCoR/HDAC3/PGC1β coactivator complex. Receptor-specific utilization of TNF receptor-associated factor 6 (TRAF6) and downstream activation of extracellular signal-regulated kinase 1 (ERK1) and TANK-binding kinase 1 (TBK1) accounts for the common ability of RANK and TLR4 to drive assembly of an NCoR/HDAC3/PGC1β complex in macrophages. ERK1, the p65 component of NFκB, and the p300 histone acetyltransferase (HAT) are also components of the induced complex and are associated with local histone acetylation and transcriptional activation of TLR4-dependent enhancers and promoters. These observations identify a TLR4/TRAF6-dependent signaling pathway that converts NCoR from a corepressor of nuclear receptors to a coactivator of NFκB and AP-1 that may be relevant to functions of NCoR in other developmental and homeostatic processes.

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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation

Project description:A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation

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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ATAC]

Project description:A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ATAC]

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Project description:A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [RNA-seq]

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A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ChIP-seq]

Project description:A TLR4/Traf6-dependent signaling pathway mediates NCoR co-activator complex formation for inflammatory gene activation [ChIP-seq]

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