Methylation-dependent regulation of hypoxia inducible factor-1 alpha gene expression by the transcription factor Kaiso. Pierre, C. C., Longo, J., Bassey-Archibong, B. I., Hallett, R. M., Milosavljevic, S., Beatty, L., Hassell, J. A., & Daniel, J. M. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1849(12):1432–1441, December, 2015.
Methylation-dependent regulation of hypoxia inducible factor-1 alpha gene expression by the transcription factor Kaiso [link]Paper  doi  abstract   bibtex   
Low oxygen tension (hypoxia) is a common characteristic of solid tumors and strongly correlates with poor prognosis and resistance to treatment. In response to hypoxia, cells initiate a cascade of transcriptional events regulated by the hypoxia inducible factor-1 (HIF-1) heterodimer. Since the oxygen-sensitive HIF-1α subunit is stabilized during hypoxia, it functions as the regulatory subunit of the protein. To date, while the mechanisms governing HIF-1α protein stabilization and function have been well studied, those governing HIF1A gene expression are not fully understood. However, recent studies have suggested that methylation of a HIF-1 binding site in the HIF1A promoter prevents its autoregulation. Here we report that the POZ-ZF transcription factor Kaiso modulates HIF1A gene expression by binding to the methylated HIF1A promoter in a region proximal to the autoregulatory HIF-1 binding site. Interestingly, Kaiso's regulation of HIF1A occurs primarily during hypoxia, which is consistent with the finding that Kaiso protein levels peak after 4 h of hypoxic incubation and return to normoxic levels after 24 h. Our data thus support a role for Kaiso in fine-tuning HIF1A gene expression after extended periods of hypoxia.
@article{pierre_methylation-dependent_2015,
	title = {Methylation-dependent regulation of hypoxia inducible factor-1 alpha gene expression by the transcription factor {Kaiso}},
	volume = {1849},
	issn = {18749399},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26514431 https://linkinghub.elsevier.com/retrieve/pii/S1874939915002308},
	doi = {10.1016/j.bbagrm.2015.10.018},
	abstract = {Low oxygen tension (hypoxia) is a common characteristic of solid tumors and strongly correlates with poor prognosis and resistance to treatment. In response to hypoxia, cells initiate a cascade of transcriptional events regulated by the hypoxia inducible factor-1 (HIF-1) heterodimer. Since the oxygen-sensitive HIF-1α subunit is stabilized during hypoxia, it functions as the regulatory subunit of the protein. To date, while the mechanisms governing HIF-1α protein stabilization and function have been well studied, those governing HIF1A gene expression are not fully understood. However, recent studies have suggested that methylation of a HIF-1 binding site in the HIF1A promoter prevents its autoregulation. Here we report that the POZ-ZF transcription factor Kaiso modulates HIF1A gene expression by binding to the methylated HIF1A promoter in a region proximal to the autoregulatory HIF-1 binding site. Interestingly, Kaiso's regulation of HIF1A occurs primarily during hypoxia, which is consistent with the finding that Kaiso protein levels peak after 4 h of hypoxic incubation and return to normoxic levels after 24 h. Our data thus support a role for Kaiso in fine-tuning HIF1A gene expression after extended periods of hypoxia.},
	number = {12},
	journal = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},
	author = {Pierre, Christina C. and Longo, Joseph and Bassey-Archibong, Blessing I. and Hallett, Robin M. and Milosavljevic, Snezana and Beatty, Laura and Hassell, John A. and Daniel, Juliet M.},
	month = dec,
	year = {2015},
	pmid = {26514431},
	keywords = {Kaiso, POZ-ZF, DNA methylation, HIF-1, Hypoxia, Transcription factor, Transcription regulation},
	pages = {1432--1441},
}
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