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Ghosh, S and Paul, A and Sen, E (2013) TNFα induced HIF-1α-β catenin axis regulates MHC class I gene activation through chromatin remodelling. Mol Cell Biol., 33 (14). pp. 2718-2731.

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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.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Mr D.D. Lal
Date Deposited: 06 Jul 2017 06:17
Last Modified: 08 Aug 2017 05:27
URI: http://nbrc.sciencecentral.in/id/eprint/148

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