Changes in developmental state: demolish the old to construct the new.

Development, along with other cellular changes of state, can be conceived as the sequential adoption of stable, epigenetically determined patterns of gene expression. The article by Laney and Hochstrasser (2003) in this issue is the most recent to exploit the Saccharomyces cerevisiae mating-type system to characterize molecular mechanisms that act when cells change gene expression and cellular state. They examine the relationship between transcriptional regulators of mating type and components of the ubiquitin-mediated protein degradation pathway, and demonstrate that proteolysis is required not only to end one program of gene expression, but also to prevent an erroneous subsequent transcriptional state. Laney and Hochstrasser (2003) conclude that ubiquitin-mediated proteolysis of the Mat 2 transcriptional repressor is fundamentally required for the developmental transition that is the yeast mating-type switch. Their work is dedicated to the memory of Ira Herskowitz, and this is a fitting tribute because he did so much to further our understanding of mating-type switching and the regulation of mating type by regulatory factors. Herskowitz coined the term “master regulatory” gene (Herskowitz 1985) and applied it to the regulators of mating type; this term has also been adopted for critical transcriptional regulators in metazoan development (Weintraub et al. 1989; Baker 2001).

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