Integrative Map of HIF1A Regulatory Elements and Variations
Abstract
:1. Introduction
2. Materials and Methods
3. Results and Discussion
3.1. Characteristics of the HIF1A Gene
3.2. Genetic Variability of the HIF1A Gene
3.3. A Map of HIF Regulatory Elements
3.3.1. HIF Target Genes
3.3.2. Upstream Regulation of HIF1A Signaling
3.3.3. Epigenomics
3.3.4. MicroRNA Regulation
3.3.5. Protein Interactions
3.3.6. Post-Translational Modifications (PTMs)
3.4. Association of HIF1A with Diseases
3.5. Future Developments
- Update of the review on associations between HIF genes and diseases.
- Development of a catalog of regulatory elements regulating HIF1A expression (upstream regulators).
- Update of the catalog of reported HIF1A target genes (downstream signaling cascades).
- Identification of novel HIF1A target genes.
- Multi-omics view in understanding HIF1A regulation, including genomics–DNA level, transcriptomics–RNA level, proteomics, glycomics, epigenomics, and miRNomics.
- Identification of therapeutic strategies targeting the HIF signaling pathway for therapy in various diseases, including cancer.
- Analysis of potential functional effect of polymorphisms located within sites of HIF1A protein hydroxylation and methylation.
4. Conclusions
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wang, G.L.; Jiang, B.H.; Rue, E.A.; Semenza, G.L. Hypoxia-inducible factor-1 is a basic-helix-loop-helix-pas heterodimer regulated by cellular o-2 tension. Proc. Natl. Acad. Sci. USA 1995, 92, 5510–5514. [Google Scholar] [CrossRef] [Green Version]
- Semenza, G.L. A compendium of proteins that interact with HIF-1α. Exp. Cell Res. 2017, 356, 128–135. [Google Scholar] [CrossRef] [PubMed]
- Li, T.; Mao, C.; Wang, X.; Shi, Y.; Tao, Y. Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation. J. Exp. Clin. Cancer Res. 2020, 39, 224. [Google Scholar] [CrossRef] [PubMed]
- Semenza, G.L. The Genomics and Genetics of Oxygen Homeostasis. Annu. Rev. Genom. Hum. Genet 2020, 21, 183–204. [Google Scholar] [CrossRef] [Green Version]
- Ivan, M.; Kondo, K.; Yang, H.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J.M.; Lane, W.S.; Kaelin, W.G. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 2001, 292, 464–468. [Google Scholar] [CrossRef] [PubMed]
- Masoud, G.N.; Li, W. HIF-1α pathway: Role, regulation and intervention for cancer therapy. Acta Pharm. Sin. B 2015, 5, 378–389. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kristan, A.; Debeljak, N.; Kunej, T. Genetic variability of hypoxia-inducible factor alpha (HIFA) genes in familial erythrocytosis: Analysis of the literature and genome databases. Eur. J. Haematol. 2019, 103, 287–299. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Semenza, G.L. HIF-1: Upstream and downstream of cancer metabolism. Curr. Opin. Genet. Dev. 2010, 20, 51–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaelin, W.G.; Ratcliffe, P.J. Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway. Mol. Cell 2008, 30, 393–402. [Google Scholar] [CrossRef]
- Gladek, I.; Ferdin, J.; Horvat, S.; Calin, G.A.; Kunej, T. HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies. Genes Chromosomes Cancer 2017, 56, 439–452. [Google Scholar] [CrossRef]
- Wei, J.; Yang, Y.; Lu, M.; Lei, Y.; Xu, L.; Jiang, Z.; Xu, X.; Guo, X.; Zhang, X.; Sun, H.; et al. Recent Advances in the Discovery of HIF-1α-p300/CBP Inhibitors as Anti-Cancer Agents. Mini Rev. Med. Chem. 2018, 18, 296–309. [Google Scholar] [CrossRef] [PubMed]
- Pirih, N.; Kunej, T. Toward a Taxonomy for Multi-Omics Science? Terminology Development for Whole Genome Study Approaches by Omics Technology and Hierarchy. Omics J. Integr. Biol. 2017, 21, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Ivan, M.; Huang, X. miR-210: Fine-tuning the hypoxic response. Adv. Exp. Med. Biol. 2014, 772, 205–227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Howe, K.L.; Achuthan, P.; Allen, J.; Alvarez-Jarreta, J.; Amode, M.R.; Armean, I.M.; Azov, A.G.; Bennett, R.; Bhai, J.; Billis, K.; et al. Ensembl 2021. Nucleic Acids Res. 2021, 49, D884–D891. [Google Scholar] [CrossRef]
- Chou, C.H.; Shrestha, S.; Yang, C.D.; Chang, N.W.; Lin, Y.L.; Liao, K.W.; Huang, W.C.; Sun, T.H.; Tu, S.J.; Lee, W.H.; et al. miRTarBase update 2018: A resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018, 46, D296–D302. [Google Scholar] [CrossRef] [PubMed]
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13, 2498–2504. [Google Scholar] [CrossRef]
- Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019, 47, D607–D613. [Google Scholar] [CrossRef] [Green Version]
- Li, L.C.; Dahiya, R. MethPrimer: Designing primers for methylation PCRs. Bioinformatics 2002, 18, 1427–1431. [Google Scholar] [CrossRef] [Green Version]
- Tate, J.G.; Bamford, S.; Jubb, H.C.; Sondka, Z.; Beare, D.M.; Bindal, N.; Boutselakis, H.; Cole, C.G.; Creatore, C.; Dawson, E.; et al. COSMIC: The Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 2019, 47, D941–D947. [Google Scholar] [CrossRef] [Green Version]
- Ruzicka, L.; Howe, D.G.; Ramachandran, S.; Toro, S.; Van Slyke, C.E.; Bradford, Y.M.; Eagle, A.; Fashena, D.; Frazer, K.; Kalita, P.; et al. The Zebrafish Information Network: New support for non-coding genes, richer Gene Ontology annotations and the Alliance of Genome Resources. Nucleic Acids Res. 2019, 47, D867–D873. [Google Scholar] [CrossRef]
- Smith, J.R.; Hayman, G.T.; Wang, S.J.; Laulederkind, S.J.F.; Hoffman, M.J.; Kaldunski, M.L.; Tutaj, M.; Thota, J.; Nalabolu, H.S.; Ellanki, S.L.R.; et al. The Year of the Rat: The Rat Genome Database at 20: A multi-species knowledgebase and analysis platform. Nucleic Acids Res. 2020, 48, D731–D742. [Google Scholar] [CrossRef]
- Bult, C.J.; Blake, J.A.; Smith, C.L.; Kadin, J.A.; Richardson, J.E. Mouse Genome Database (MGD) 2019. Nucleic Acids Res. 2019, 47, D801–D806. [Google Scholar] [CrossRef] [Green Version]
- Chen, F.; Chandrashekar, D.S.; Varambally, S.; Creighton, C.J. Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers. Nat. Commun. 2019, 10, 5679. [Google Scholar] [CrossRef] [Green Version]
- Chandrashekar, D.S.; Bashel, B.; Balasubramanya, S.A.H.; Creighton, C.J.; Ponce-Rodriguez, I.; Chakravarthi, B.; Varambally, S. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia 2017, 19, 649–658. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015, 4. [Google Scholar] [CrossRef] [PubMed]
- Semenza, G.L. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J. Clin. Investig. 2013, 123, 3664–3671. [Google Scholar] [CrossRef] [Green Version]
- Hayashi, Y.; Yokota, A.; Harada, H.; Huang, G. Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1α in cancer. Cancer Sci. 2019, 110, 1510–1517. [Google Scholar] [CrossRef] [Green Version]
- Slemc, L.; Kunej, T. Transcription factor HIF1A: Downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature. Tumour. Biol. 2016, 37, 14851–14861. [Google Scholar] [CrossRef] [PubMed]
- Ferdin, J.; Nishida, N.; Wu, X.; Nicoloso, M.S.; Shah, M.Y.; Devlin, C.; Ling, H.; Shimizu, M.; Kumar, K.; Cortez, M.A.; et al. HINCUTs in cancer: Hypoxia-induced noncoding ultraconserved transcripts. Cell Death Differ. 2013, 20, 1675–1687. [Google Scholar] [CrossRef] [Green Version]
- Serocki, M.; Bartoszewska, S.; Janaszak-Jasiecka, A.; Ochocka, R.J.; Collawn, J.F.; Bartoszewski, R. miRNAs regulate the HIF switch during hypoxia: A novel therapeutic target. Angiogenesis 2018, 21, 183–202. [Google Scholar] [CrossRef] [Green Version]
- Li, C.; Xiong, W.; Liu, X.; Xiao, W.; Guo, Y.; Tan, J.; Li, Y. Hypomethylation at non-CpG/CpG sites in the promoter of HIF-1α gene combined with enhanced H3K9Ac modification contribute to maintain higher HIF-1α expression in breast cancer. Oncogenesis 2019, 8, 26. [Google Scholar] [CrossRef]
- Mariani, C.J.; Vasanthakumar, A.; Madzo, J.; Yesilkanal, A.; Bhagat, T.; Yu, Y.; Bhattacharyya, S.; Wenger, R.H.; Cohn, S.L.; Nanduri, J.; et al. TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Rep. 2014, 7, 1343–1352. [Google Scholar] [CrossRef] [Green Version]
- Bao, L.; Chen, Y.; Lai, H.T.; Wu, S.Y.; Wang, J.E.; Hatanpaa, K.J.; Raisanen, J.M.; Fontenot, M.; Lega, B.; Chiang, C.M.; et al. Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration. Nucleic Acids Res. 2018, 46, 6576–6591. [Google Scholar] [CrossRef] [Green Version]
- Perez-Perri, J.I.; Dengler, V.L.; Audetat, K.A.; Pandey, A.; Bonner, E.A.; Urh, M.; Mendez, J.; Daniels, D.L.; Wappner, P.; Galbraith, M.D.; et al. The TIP60 Complex Is a Conserved Coactivator of HIF1A. Cell Rep. 2016, 16, 37–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Albanese, A.; Daly, L.A.; Mennerich, D.; Kietzmann, T.; Sée, V. The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity. Int. J. Mol. Sci. 2020, 22, 268. [Google Scholar] [CrossRef] [PubMed]
- Tomc, J.; Debeljak, N. Molecular Pathways Involved in the Development of Congenital Erythrocytosis. Genes 2021, 12, 1150. [Google Scholar] [CrossRef]
- Camps, C.; Petousi, N.; Bento, C.; Cario, H.; Copley, R.R.; McMullin, M.F.; van Wijk, R.; Ratcliffe, P.J.; Robbins, P.A.; Taylor, J.C.; et al. Gene panel sequencing improves the diagnostic work-up of patients with idiopathic erythrocytosis and identifies new mutations. Haematologica 2016, 101, 1306–1318. [Google Scholar] [CrossRef] [PubMed]
- Torti, L.; Teofili, L.; Capodimonti, S.; Nuzzolo, E.R.; Iachininoto, M.G.; Massini, G.; Coluzzi, S.; Tafuri, A.; Fiorin, F.; Girelli, G.; et al. Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors. Blood Transfus. 2013, 11, 553–557. [Google Scholar] [CrossRef] [PubMed]
- Percy, M.J.; Mooney, S.M.; McMullin, M.F.; Flores, A.; Lappin, T.R.; Lee, F.S. A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation. Mol. Cancer 2003, 2, 31. [Google Scholar] [CrossRef] [Green Version]
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Kunej, T. Integrative Map of HIF1A Regulatory Elements and Variations. Genes 2021, 12, 1526. https://doi.org/10.3390/genes12101526
Kunej T. Integrative Map of HIF1A Regulatory Elements and Variations. Genes. 2021; 12(10):1526. https://doi.org/10.3390/genes12101526
Chicago/Turabian StyleKunej, Tanja. 2021. "Integrative Map of HIF1A Regulatory Elements and Variations" Genes 12, no. 10: 1526. https://doi.org/10.3390/genes12101526