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We investigated hypoxia-inducible factor (HIF)-dependent changes in the expression of 5592 genes in response to hypoxia (0.1% O2, 16 h) by per-forming cDNA microarray analyses of mouse hepa1c1c7 and BpRc1 cells. BpRc1 cells are a hepa1c1c7 variant defective in HIF-b⁄aryl hydrocarbon receptor nuclear translocator (Arnt), and are therefore unable to induce HIF target genes in response to hypoxia. | ễFEBS Journal Microarray analyses of hypoxia-regulated genes in an aryl hydrocarbon receptor nuclear translocator Arnt -dependent manner Su Mi Choi Hookeun Oh and Hyunsung Park Department of Life Science University of Seoul South Korea Keywords Arnt gene expression HIF hypoxia microarray Correspondence H. Park Department of Life Science University of Seoul 90 Jeonnong-dong Dongdaemun-gu Seoul130-743 South Korea Fax 82 2 2210 2888 Tel 82 2 2210 2622 E-mail hspark@uos.ac.kr These authors made equal contributions to this study Received 17 July 2008 revised 12 September 2008 accepted 17 September 2008 doi 10.1111 j.1742-4658.2008.06686.x We investigated hypoxia-inducible factor HIF -dependent changes in the expression of 5592 genes in response to hypoxia 0.1 O2 16 h by performing cDNA microarray analyses of mouse hepa1c1c7 and BpRc1 cells. BpRc1 cells are a hepa1c1c7 variant defective in HIF-p aryl hydrocarbon receptor nuclear translocator Arnt and are therefore unable to induce HIF target genes in response to hypoxia. By comparing hepa1c1c7 cells with BpRc1 cells we were able to investigate hypoxia-regulated gene expression as well as the role played by HIF in regulating the hypoxic-dependent response of gene expression. This study identified 50 hypoxia-induced genes and 36 hypoxia-repressed genes. Quantitative PCR analysis of nine genes confirmed our ability to accurately analyze changes in hypoxia-induced gene expression by microarray analysis. By comparing quantitative PCR analyses of these nine genes in BpRc1 and hepa1c1c7 cells we determined that eight of the nine hypoxia-induced genes are Arnt dependent. Additional quantitative PCR analyses of eight hypoxia-repressed genes confirmed with a 50 probability that microarray analysis was able to predict hypoxia-repressed gene expression. Only two of the four confirmed genes were found to be repressed in an Arnt-dependent manner. Collectively six of these 13 genes 46.2 probability showed a pattern of expression .
