التفاصيل البيبلوغرافية
| العنوان: |
Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions |
| المؤلفون: |
Martí, J.M., Garcia-Diaz, A., Delgado-Bellido, D., O'Valle, F., González-Flores, A., Carlevaris, O., Rodríguez-Vargas, J.M., Amé, J.C., Dantzer, F., King, G.L., Dziedzic, K., Berra, E., de Álava, E., Amaral, A.T., Hammond, E.M., Oliver, F.J. |
| المصدر: |
Redox Biology, 41, 101885, (2021-02-01) |
| بيانات النشر: |
Zenodo |
| سنة النشر: |
2021 |
| المجموعة: |
Zenodo |
| مصطلحات موضوعية: |
ChIP-seq, Hypoxia, PARP-1, PARylation, Tumor microenvironment |
| الوصف: |
Background: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded. Methods: In this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes. Results: In human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a reduced fitness during hypoxic induction. Conclusions: These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α over-activation. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
https://zenodo.org/communities/cicbiogune_repo; https://doi.org/10.1016/j.redox.2021.101885; oai:zenodo.org:4904832 |
| DOI: |
10.1016/j.redox.2021.101885 |
| الاتاحة: |
https://doi.org/10.1016/j.redox.2021.101885 |
| Rights: |
info:eu-repo/semantics/openAccess ; Creative Commons Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/legalcode |
| رقم الانضمام: |
edsbas.E7A681CE |
| قاعدة البيانات: |
BASE |