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- W2149691945 abstract "Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in the progression of glioblastoma multiforme tumors, which are characterized by their effective immune escape mechanisms. As major histocompatibility complex class I (MHC-I) is involved in glioma immune evasion and since HIF-1α is a pivotal link between inflammation and glioma progression, the role of tumor necrosis factor alpha (TNF-α)-induced inflammation in MHC-I gene regulation was investigated. A TNF-α-induced increase in MHC-I expression and transcriptional activation was concurrent with increased HIF-1α, ΝF-κΒ, and β-catenin activities. While knockdown of HIF-1α and β-catenin abrogated TNF-α-induced MHC-I activation, NF-κB had no effect. β-Catenin inhibition abrogated HIF-1α activation and vice versa, and this HIF-1α-β-catenin axis positively regulated CREB phosphorylation. Increased CREB activation was accompanied by its increased association with β-catenin and CBP. Chromatin immunoprecipitation revealed increased CREB enrichment at CRE/site α on the MHC-I promoter in a β-catenin-dependent manner. β-Catenin replaced human Brahma (hBrm) with Brg1 as the binding partner for CREB at the CRE site. The hBrm-to-Brg1 switch is crucial for MHC-I regulation, as ATPase-deficient Brg1 abolished TNF-α-induced MHC-I expression. β-Catenin also increased the association of MHC-I enhanceosome components RFX5 and NF-YB at the SXY module. CREB acts as a platform for assembling coactivators and chromatin remodelers required for MHC-I activation in a HIF-1α/β-catenin-dependent manner." @default.
- W2149691945 created "2016-06-24" @default.
- W2149691945 creator A5000272358 @default.
- W2149691945 creator A5019979649 @default.
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- W2149691945 date "2013-07-01" @default.
- W2149691945 modified "2023-10-16" @default.
- W2149691945 title "Tumor Necrosis Factor Alpha-Induced Hypoxia-Inducible Factor 1α–β-Catenin Axis Regulates Major Histocompatibility Complex Class I Gene Activation through Chromatin Remodeling" @default.
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- W2149691945 doi "https://doi.org/10.1128/mcb.01254-12" @default.
- W2149691945 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3700138" @default.
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