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Originally published as Genetics Published Articles Ahead of Print on January 21, 2007.
Genetics, Vol. 175, 1127-1135, March 2007, Copyright © 2007
doi:10.1534/genetics.106.068932
Glucose-Responsive Regulators of Gene Expression in Saccharomyces cerevisiae Function at the Nuclear Periphery via a Reverse Recruitment Mechanism
Nayan J. Sarma, Terry M. Haley, Kellie E. Barbara, Thomas D. Buford, Kristine A. Willis and George M. Santangelo1
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi 39406
1 Corresponding author: Department of Biological Sciences, University of Southern Mississippi, 118 College Dr., No. 5018, Hattiesburg, MS 39406.
E-mail: george.santangelo{at}usm.edu
Regulation of gene transcription is a key feature of developmental, homeostatic, and oncogenic processes. The reverse recruitment model of transcriptional control postulates that eukaryotic genes become active by moving to contact transcription factories at nuclear substructures; our previous work showed that at least some of these factories are tethered to nuclear pores. We demonstrate here that the nuclear periphery is the site of key events in the regulation of glucose-repressed genes, which together compose one-sixth of the Saccharomyces cerevisiae genome. We also show that the canonical glucose-repressed gene SUC2 associates tightly with the nuclear periphery when transcriptionally active but is highly mobile when repressed. Strikingly, SUC2 is both derepressed and confined to the nuclear rim in mutant cells where the Mig1 repressor is nuclear but not perinuclear. Upon derepression all three subunits (
, ß, and 
) of the positively acting Snf1 kinase complex localize to the nuclear periphery, resulting in phosphorylation of Mig1 and its export to the cytoplasm. Reverse recruitment therefore appears to explain a fundamental pathway of eukaryotic gene regulation.
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