Dual regulation of the met4 transcription factor by ubiquitin-dependent degradation and inhibition of promoter recruitment.
The ubiquitin system has been recently implicated in various aspects of transcriptional regulation, including proteasome-dependent degradation of transcriptional activators. In yeast, the activator Met4 is inhibited by the SCF(Met30) ubiquitin ligase, which recognizes and oligo-ubiquitylates Met4. Here, we demonstrate that in minimal media, Met4 is ubiquitylated and rapidly degraded in response to methionine excess, whereas in rich media, Met4 is oligo-ubiquitylated but remains stable. In the latter growth condition, oligo-ubiquitylated Met4 is not recruited to MET gene promoters, but is recruited to the SAM genes, which are required for production of S-adenosylmethionine, an unstable metabolite that is not present in rich medium. Thus, ubiquitylation not only regulates Met4 by distinct degradation-dependent and -independent mechanisms, but also controls differential recruitment of a single transcription factor to distinct promoters, thereby diversifying transcriptional activator specificity.
Kuras
Laurent
L
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvettte, France.
Rouillon
Astrid
A
Lee
Traci
T
Barbey
Regine
R
Tyers
Mike
M
Thomas
Dominique
D
D050976:Basic-Leucine Zipper Transcription Factors; D015153:Blotting, Western; D002455:Cell Division; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D008715:Methionine / Q000494:pharmacology; D010453:Peptide Synthases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D003470:Culture Media; D004268:DNA-Binding Proteins; C073675:MET4 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D025801:Ubiquitin; D008715:Methionine; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases