"(T)he truth of a theory lies in the deductive methods used to establish it and the experimental demonstration of its fundamental premises and consequences." - Jacques Monod I had the good fortune, early on, to be gripped by a scientific problem - gene regulation - that had ramifications beyond what I imagined. Its unfoldings have kept me enthralled ever since. We began with bacteria - and especially with bacteriophage lambda (lambda) - and then moved to work with yeast and mammalian cells. We always sought coherent descriptions, ideas that would apply to apparently disparate cases - regulation of prokaryotic and eukaryotic genes, for example, despite the fact that the latter, but not the former, are sequestered in a nucleus and wrapped in nucleosomes. My goal here is to put the various stages of our understanding, from the beginning of my involvement, in an overarching context. I might not say anything that has not been said by others or me, but my hope is that otherwise obscure connections and simplifications will be made clear. I hope I avoid distortions, but I cannot cite all the important contributions of others. More detailed explanations for various experiments and arguments, along with more extensive references, can be found in my two books and in the references here (1, 2). Where I refer to "we", I of course mean to include the crucial roles of this or that student or postdoctoral fellow. They are identified in the reference list but not in the text.

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Ptashne M

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