The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Differential Regulation of the Transcriptional Activities of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) and HIF-2α in Stem Cells
Abstract
Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible factors (HIFs), HIF-1alpha and HIF-2alpha. The HIF-1alpha and HIF-2alpha subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains, implying they may have unique target genes and require distinct transcriptional cofactors. Our previous results demonstrated that HIF-1alpha and HIF-2alpha regulate distinct target genes. Here, we report that HIF-2alpha is not transcriptionally active in embryonic stem (ES) cells, as well as possible inhibition by a HIF-2alpha-specific transcriptional repressor. Using DNA microarray analysis of hypoxia-inducible genes in wild-type (WT), Hif-1alpha(-)(/)(-), and Hif-2alpha(-)(/)(-) ES cells, we show that HIF-1alpha induces a large number of both confirmed and novel hypoxia-inducible genes, while HIF-2alpha does not activate any of its previously described targets. We further demonstrate that inhibition of HIF-2alpha function occurs at the level of transcription cofactor recruitment to endogenous target gene promoters. Overexpression of WT and, notably, a DNA-binding-defective HIF-2alpha mutant restores endogenous HIF-2alpha protein activity, suggesting that ES cells express a HIF-2alpha-specific corepressor that can be titrated by overexpressed HIF-2alpha protein. HIF-2alpha repression may explain why patients with mutations in the VHL tumor suppressor gene display cancerous lesions in specific tissue types.
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Citations
Cites
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · cited 2×
“HIF activation by hypoxia ( 5% O2) is regulated at the level of -subunit protein stability in an oxygen-dependent fashion (41).”
BackgroundHIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Self-citationTian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351
Raval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865
Maltepe, E., Schmidt, J. V., Baunoch, D., Bradfield, C. A., & Simon, M. C. (1997) · Nature · doi:10.1038/386403a0 · Cited by 781
Self-citation
Cited by
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251
Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones-Hinojosa, A. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.07.007 · Cited by 1,535
Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells
Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., Shi, Q., Cao, Y., Lathia, J., McLendon, R. E., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.018 · Cited by 1,354
A MicroRNA Signature of Hypoxia
Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055
The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α
Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., Guimaraes, A., Marinelli, B., Wikstrom, J. D., Nir, T., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.041 · Cited by 1,001
Metadata
- Authors
- Hu, C.-J., Iyer, S., Sataur, A., Covello, K. L., Chodosh, L. A., & Simon, M. C.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-05-01
- Volume
- 26
- Issue
- 9
- Pages
- 3514-3526
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2144137526
- Cited by
- 266
- References
- 18
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hu, C.-J., Iyer, S., Sataur, A., Covello, K. L., Chodosh, L. A., & Simon, M. C. (2006). Differential Regulation of the Transcriptional Activities of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) and HIF-2α in Stem Cells. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.26.9.3514-3526.2006
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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