Mark Ptashne

..We find that there is an optimal linker length which separates the DNA and the activation region for transcription activation...

..This system of regulation is highly 'evolvable', and its use accounts, at least in part, for the nature of the complexities observed in biological systems...

..This memory is conveyed by a cytoplasmically transmitted galactokinase working as a signal transducer...

..These are examples of 'regulatory' decisions. A rather simple mechanism - called regulated recruitment - lies at the heart of many of these regulatory decisions...

..This system of regulation is highly 'evolvable'. Its use accounts, at least in part, for the nature of many of the complexities observed in biological systems...

..Higher eukaryotic RSC lacks the specific DNA-binding determinants found on yeast RSC, and evidently Gal4 works in those organisms despite whatever obstacle broadly positioned nucleosomes present...

..These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field...

..Our results are consistent with the notion that a single species of activator, Gal4, separately contacts, and thereby directly recruits, SAGA and Mediator...

..The results are consistent with the finding that the classical activator Gal4, working at the GAL1 promoter, activates transcription by (at least in part) independently recruiting SAGA and Mediator...

..Removal of promoter-bound nucleosomes is delayed in a chaperone mutant, and our findings suggest an involvement of HSP90 and HSP70 in this early step in gene induction...

..As this occupancy is increased (by sequence alteration), nucleosome removal upon induction is decreased, as is mRNA production. These results explain why promoter sequences have evolved to form nucleosomes relatively inefficiently...

..The interaction evidently positions each activator, as it activates transcription, so that it gets phosphorylated by SRB10, and thus a common mechanism targets disparate substrates to the kinase...

..All three are unstable, and for the case analyzed in detail, stabilization decreases activity. Thus, to the extent tested, both classical and nonclassical activators work most efficiently when proteolytically unstable...

..These nucleosomes, evidently, inhibit basal transcription but are poised to be removed quickly upon command...

..The resulting hybrid phage is viable, but a subtle phenotypic defect explains a puzzle concerning the workings of the switch...

..Multiple negative and positive 'add-ons', often with small individual effects, make elementary systems that work, work better. Cancer illustrates various of these fundamental processes gone awry...

..P201, unlike the typical yeast acidic activating region, does not work in mammalian cells, which is consistent with the notion that the unique target of P201 (Gal11) is absent from mammalian cells...

..Here I wish to probe our use of language in this way, and to show how such a discussion leads to some more general considerations concerning gene regulation...

..These and additional results, including those of others, clarify how disparate activators can work at many different promoters...

..These and other results indicate that DNA-tethered Tup1 represses by interacting with some component of the transcriptional machinery binding to the promoter, an interaction that is facilitated by the preformed loop at the telomere...

..In some cases, residues within the activating regions are also phosphorylated. The results define a mechanism by which a kinase is recruited to alternate substrates with diverse physiological consequences...

..The result shows that although all natural activating regions characterized thus far are peptidic, this function can be served by other kinds of moieties as well...

..In particular we are testing the idea that this protein, a component of the large complex called the Mediator, is rapidly degraded in cells, and that this instability facilitates activation of transcription ..

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..The role of nucleosomes in helping and hindering gene activation will be analyzed using these two classes of activators; and the mechanism of overcoming the inhibitory effect of nucleosomes will be explored. ..

..In particular we are testing the idea that this protein, a component of the large complex called the Mediator, is rapidly degraded in cells, and that this instability facilitates activation of transcription ..