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

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

Bridget L. Todd; Emerson V. Stewart; John S. Burg; Adam L. Hughes; Peter J. Espenshade

2006

Scholarcy highlights

  • Fission yeast sterol regulatory element binding protein, called Sre1p, functions in an oxygen-sensing pathway to allow adaptation to fluctuating oxygen concentrations
  • To determine if yeast Sre1p could recognize the same sequence as mammalian SREBP, we examined whether Sre1p could bind the human LDL receptor SRE or a mutant SRE
  • This study presents the first genome-wide analysis of anaerobic gene expression in fission yeast and reveals that ∼25% of the genome is differentially regulated 1.5 h after a shift to anaerobic conditions
  • Multiple lines of evidence indicate that Sre1p is a principal regulator of this early transcriptional response to low oxygen: sre1+ is essential for cell growth at early times after a shift to anaerobic conditions, Sre1p is required for anaerobic induction of 44/65 genes whose expression increases ≥2-fold anaerobically in wild-type cells, Sre1p binds to anaerobically induced gene promoters in vivo, and Sre1p binds in vitro to two DNA elements required for oxygen-dependent transcription
  • To identify physiological Sre1p target genes, we examined gene expression in wild-type and sre1Δ cells after cells were shifted to anaerobic conditions for 1.5 h
  • To allow a comparison of wild-type and sre1Δ cells, Sre1p was activated by growth at 0.2% oxygen rather than under anaerobic conditions. sre1Δ cells showed no growth defect at 0.2% oxygen
  • In support of this approach, preliminary experiments revealed that while the change of expression for many anaerobically induced genes is greater at 4 h than at 1.5 h, 39 environmental stress response genes are induced at 4 h but not at 1.5 h in sre1Δ cells
  • We identify the oxygen-regulated transcription factor Sre1p as a principal regulator of anaerobic gene expression in S. pombe, controlling 68% of the genes induced ≥2-fold under anaerobic conditions

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