Ubiquitin-dependent degradation of the yeast Mat(alpha)2 repressor enables a switch in developmental state.
Developmental transitions in eukaryotic cell lineages revolve around two general processes: the dismantling of the regulatory program specifying an initial differentiated state and its replacement by a new system of regulators. However, relatively little is known about the mechanisms by which a previous regulatory state is inactivated. Protein degradation is implicated in a few examples, but the molecular reasons that a formerly used regulator must be removed are not understood. Many yeast strains undergo a developmental transition in which cells of one mating type differentiate into a distinct cell type by a programmed genetic rearrangement at the MAT locus. We find that Mat(alpha)2, a MAT-encoded transcriptional repressor that is key to creating several cell types, must be rapidly degraded for cells to switch their mating phenotype properly. Strikingly, ubiquitin-dependent proteolysis of alpha2 is required for two mechanistically distinct purposes: It allows the timely inactivation of one transcriptional repressor complex, and it prevents the de novo assembly of a different, inappropriate regulatory complex. Analogous epigenetic mechanisms for reprogramming transcription are likely to operate in many developmental pathways.
Laney
Jeffrey D
JD
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.
Hochstrasser
Mark
M
D002352:Carrier Proteins / Q000378:metabolism; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D018398:Homeodomain Proteins / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes
D002352:Carrier Proteins; D018398:Homeodomain Proteins; C062928:MATA2 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C066752:UBC1 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases