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The Octamer Binding Transcription Factor Oct-1 Is a Stress Sensor

¹ Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts and Departments of ² Medicine and ³ Biochemistry, Microbiology, and Immunology, University of Ottawa, The Ottawa Health Science Research Institute, Ottawa, Ontario, Canada

Requests for reprints: Phillip A. Sharp, Center for Cancer Research, Massachusetts Institute of Technology, Room E17-529, 77 Massachusetts Avenue, Cambridge, MA 02139-4307. Phone: 617-253-6421; Fax: 617-253-3867; E-mail: sharppa{at}mit.edu.

The POU-domain transcription factor Oct-1 is widely expressed in adult tissues and has been proposed to regulate a large group of target genes. Microarray expression profiling was used to evaluate gene expression changes in Oct-1-deficient mouse fibroblasts. A number of genes associated with cellular stress exhibited altered expression. Consistent with this finding, Oct-1-deficient fibroblasts were hypersensitive to radiation, doxorubicin, and hydrogen peroxide and harbored elevated reactive oxygen species. Expression profiling identified a second group of genes dysregulated in Oct-1-deficient fibroblasts following irradiation, including many associated with oxidative and metabolic stress. A number of these genes contain octamer sequences in their immediate 5' regulatory regions, some of which are conserved in human. These results indicate that Oct-1 modulates the activity of genes important for the cellular response to stress.

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