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Molecular and Cellular Biology, April 2006, p. 2817-2831, Vol. 26, No. 7
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.7.2817-2831.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Sterol Regulatory Element Binding Protein Is a Principal Regulator of Anaerobic Gene Expression in Fission Yeast{dagger}

Bridget L. Todd, Emerson V. Stewart, John S. Burg, Adam L. Hughes, and Peter J. Espenshade*

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Received 2 August 2005/ Returned for modification 29 August 2005/ Accepted 3 January 2006

Fission yeast sterol regulatory element binding protein (SREBP), called Sre1p, functions in an oxygen-sensing pathway to allow adaptation to fluctuating oxygen concentrations. The Sre1p-Scp1p complex responds to oxygen-dependent sterol synthesis as an indirect measure of oxygen availability. To examine the role of Sre1p in anaerobic gene expression in Schizosaccharomyces pombe, we performed transcriptional profiling experiments after a shift to anaerobic conditions for 1.5 h. Of the 4,940 genes analyzed, expression levels of 521 (10.5%) and 686 (13.9%) genes were significantly increased and decreased, respectively, under anaerobic conditions. Sre1p controlled 68% of genes induced ≥2-fold. Oxygen-requiring biosynthetic pathways for ergosterol, heme, sphingolipid, and ubiquinone were primary targets of Sre1p. Induction of glycolytic genes and repression of mitochondrial oxidative phosphorylation genes largely did not require Sre1p. Using chromatin immunoprecipitation, we demonstrated that Sre1p acts directly at target gene promoters and stimulates its own transcription under anaerobic conditions. sre1+ promoter analysis identified two DNA elements that are both necessary and sufficient for oxygen-dependent, Sre1p-dependent transcription. Interestingly, these elements are homologous to sterol regulatory elements bound by mammalian SREBP, highlighting the evolutionary conservation between Sre1p and SREBP. We conclude that Sre1p is a principal activator of anaerobic gene expression, upregulating genes required for nonrespiratory oxygen consumption.

* Corresponding author. Mailing address: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Physiology 107B, Baltimore, MD 21205. Phone: (443) 287-5026. Fax: (410) 955-4129. E-mail: peter.espenshade{at}jhmi.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, April 2006, p. 2817-2831, Vol. 26, No. 7
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.7.2817-2831.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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