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Met4 Picks a Promoter

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Science's STKE  23 Jul 2002:
Vol. 2002, Issue 142, pp. tw263-TW263
DOI: 10.1126/stke.2002.142.tw263

A controversy regarding the mechanism by which ubiquitination inhibits the transcription factor Met4 in yeast exists. Both ubiquitin-mediated degradation of Met4 has been reported and a ubiquitin-mediated, but degradation-independent, inhibition of Met4 has been reported. Kuras et al. show that the degradation of Met4 in response to high levels of methionine depends on the growth medium, with yeast grown in minimal medium with high methionine showing ubiquitin-dependent degradation of Met4, and yeast grown on rich medium with or without supplemented methionine showing ubiquitylated, but stable, Met4. Chromatin immunoprecipitation assays showed that, when methionine was low, Met4 was bound to promoters of the MET gene network that synthesizes sulfur-containing amino acids, whereas when methionine was abundant (in both minimal medium supplemented with methionine and in rich medium), Met4 was not bound to these promoters. In addition to regulating the expression of the MET genes, Met4 was recruited to the promoters of genes involved in S-adenosylmethionine (SAM). In yeast grown in rich medium, Met4 was bound to the SAM1 and SAM2 promoters, whereas this binding was inhibited in yeast grown on minimal medium supplemented with methionine. Thus, the authors propose that the stable ubiquitylated Met4 present under rich medium growth conditions allows the selective recruitment of Met4 to the SAM genes, which allows the continued production of the unstable metabolite SAM under conditions in which methionine synthesis is not required.

L. Kuras, A. Rouillon, T. Lee, R. Barbey, M. Tyers, D. Thomas, Dual regulation of the Met4 transcription factor by ubiquitin-dependent degradation and inhibition of promoter recruitment. Mol. Cell 10, 69-80 (2002). [Online Journal]

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