An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia

Benita, Y., Kikuchi, H., Smith, A. D., Zhang, M. Q., Chung, D. C., Xavier, R. J. (2009) An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia. Nucleic Acids Res, 37 (14). 4587–4602.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/19491311
DOI: 10.1093/nar/gkp425

Abstract

The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > analysis and processing
bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > analysis and processing > microarray gene expression processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Zhang lab
CSHL Cancer Center Shared Resources > Bioinformatics Service
Depositing User: Matt Covey
Date Deposited: 20 Feb 2013 21:47
Last Modified: 30 Dec 2014 14:33
PMCID: PMC2724271
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27400

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