Rogerson, Connor, Sciacovelli, Marco 
ORCID: 0000-0003-2958-4292, Maddalena, Lucas A, Pouikli, Andromachi, Segarra-Mondejar, Marc, Valcarcel-Jimenez, Lorea, Schmidt, Christina, Yang, Ming, Ivanova, Elena, Kent, Joshua et al (show 5 more authors)
(2023)
FOXA2 controls the anti-oxidant response in FH-deficient cells.
CELL REPORTS, 42 (7).
112751-.
Abstract
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a cancer syndrome caused by inactivating germline mutations in fumarate hydratase (FH) and subsequent accumulation of fumarate. Fumarate accumulation leads to profound epigenetic changes and the activation of an anti-oxidant response via nuclear translocation of the transcription factor NRF2. The extent to which chromatin remodeling shapes this anti-oxidant response is currently unknown. Here, we explored the effects of FH loss on the chromatin landscape to identify transcription factor networks involved in the remodeled chromatin landscape of FH-deficient cells. We identify FOXA2 as a key transcription factor that regulates anti-oxidant response genes and subsequent metabolic rewiring cooperating without direct interaction with the anti-oxidant regulator NRF2. The identification of FOXA2 as an anti-oxidant regulator provides additional insights into the molecular mechanisms behind cell responses to fumarate accumulation and potentially provides further avenues for therapeutic intervention for HLRCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Chromatin, Humans, Leiomyomatosis, Carcinoma, Renal Cell, Skin Neoplasms, Uterine Neoplasms, Kidney Neoplasms, Neoplastic Syndromes, Hereditary, Fumarate Hydratase, Antioxidants, Female, NF-E2-Related Factor 2, Hepatocyte Nuclear Factor 3-beta |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 27 Sep 2023 10:56 |
| Last Modified: | 27 Sep 2023 10:56 |
| DOI: | 10.1016/j.celrep.2023.112751 |
| Open Access URL: | https://doi.org/10.1016/j.celrep.2023.112751 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173117 |
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