Glucose-responsive regulators of gene expression in Saccharomyces cerevisiae function at the nuclear periphery via a reverse recruitment mechanism.
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 (alpha, beta, and gamma) 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.
Sarma
Nayan J
NJ
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA.
Haley
Terry M
TM
Barbara
Kellie E
KE
Buford
Thomas D
TD
Willis
Kristine A
KA
Santangelo
George M
GM
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism* / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D018613:Microscopy, Confocal; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043324:beta-Fructofuranosidase / Q000378:metabolism*
D004268:DNA-Binding Proteins; C085976:MIG1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C468437:SUC2 protein, S cerevisiae; D043324:beta-Fructofuranosidase