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FOXA2 controls the anti-oxidant response in FH-deficient cells independent of NRF2

ABSTRACT: Hereditary Leiomyomatosis and renal cell cancer is caused by fumarate hydratase loss of heterozygosity and subsequence accumulation of fumarate. Fumarate is known to activate the anti-oxidant response and is key for cellular survival. Fumarate succinates KEAP1 which releases NRF2 to activate the antioxidant response. The role of fumarate on the global regulatory chromatin landscape is less understood. Here, by integrating chromatin accessibility and histone ChIP-seq profiles, we identify complex transcription factor networks involved in the highly remodelled chromatin landscape of FH-deficient cells. We implicate FOXA2 in the maintenance of FH-deficient cells by regulating anti-oxidant response genes and subsequent metabolic output, independent of NRF2. These results identify new redox and amino acid metabolism regulators and provide new avenues for therapeutic intervention.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Cultured Cells

DISEASE(S): Cancer

SUBMITTER: Ming Yang

PROVIDER: ST002199 | MetabolomicsWorkbench | Wed Jun 01 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench

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