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The recruitment model for gene activation stipulates that an activator works by bringing the transcriptional machinery to the DNA. Recent experiments in bacteria and yeast indicate that many genes can be activated by this mechanism. These findings have implications for our understanding of the nature of activating regions and their targets, and for the role… (More)
Proteins that activate genes are quite disparate in character; in particular, some work 'universally' and others do not. A simple model can accommodate most of the recently published results.
Retinoic acid (RA) affects the growth and differentiation of cells in culture, usually to decrease the growth rate. In amphibian limb regeneration RA has the remarkable ability to affect pattern formation by changing positional identity, but its initial action on the limb is to inhibit division of the blastemal progenitor cells. Newt limb blastemal cells… (More)
Many crucial cellular enzymes--including RNA polymerases, kinases, phosphatases, proteases, acetylaters, etc.--have multiple potential substrates. Regulation entails substrate selection, a process effected by a mechanism we call regulated localization. This formulation is particularly well illustrated by the mechanisms of gene regulation. Analysis of these… (More)
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, adult-onset motor neuron disease that arises as a dominantly inherited trait in approximately 10% of ALS cases. Mutations in one gene, cytosolic Cu/Zn superoxide dismutase (SOD1), account for approximately 25% of familial ALS (FALS) cases. We have performed a genetic linkage screen in 16… (More)
The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including the progress zone of the avian and mouse limb bud. Expression of mouse Msx-1 in a cultured myogenic cell line conferred a transformed phenotype and inhibited fusion into myotubes. It has been proposed that Msx-1 expression is required to maintain certain cells… (More)
The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to be mediated by the various retinoic acid receptors. Different receptor types are encoded by distinct genes (alpha, beta, and gamma), whereas various isoforms within each type are encoded by splicing variants resulting from the use of alternative promoters. The… (More)