Each of the billions of cell of an animal contains a kind of genetic encyclopedia of DNA which contains in small stories, or genes, the information required to make the proteins which compose that cell. What distinguishes one cell from another is how each cell reads a set of instructions before each of these information units (called genes), and uses those instructions to decide whether or not to make copy of the unit of information. These copies provide the instructions to tell cells to make the proteins which distinguish say a skin cell from a liver cell. Until our studies it was generally thought that the lifetime of each copy of an information unit in the cell was fixed. Dr. Shapiro showed that the hormone estrogen both causes the cells to copy the information units involved in the production of egg proteins and greatly increases the time the copies are present in the cell before being scrapped and destroyed. Since only copies of the information involved in egg protein production are made more stable by estrogen, a large part of our work is devoted to identifying the instructions on the copies which tell the cell to make them stable when estrogen is present. In recent work he developed a system for testing which parts of the copy are important in making them more stable, and showed that the information used to make the protein does not control the lifespan of the copy. The present proposal aims to identify more precisely the instructions in the copy which tell the cell this copy is subject to stabilization by estrogen. He will also begin studies aimed at identifying the cell proteins which read this information. Finally the mechanism by which cells sense the presence of estrogen and communicate this information to the places in the cell where the copies reside will be identified. Regulation of the lifespan of copies of genetic information has emerged as common control mechanism by hormones. Faulty regulation of the lifespan of copies has also been shown to be important in several common types of cancer. However, little is known about how the lifespan of copies of genetic information is controlled. The estrogen- mediated increase in the stability of copies of genetic information encoding egg proteins provides one of the best opportunities to learn how this important process is controlled in many systems.
