Differentiated cell types within multicellular organisms are thought to be specified by cellular epigenetic information that is stable over time and inherited in mitosis. The nature of this epigenetic information is important to an understanding of how differentiated cell types arise and are maintained. One form of epigenetic information proposed to specify differentiated cell types are steady state cellular levels of autoregulatory transcription factors. Autoregulatory transcription factors regulate the transcription of their own genes and can have multiple alternative steady state levels in the cell. Each alternative steady state level would specify a unique differentiated cell type, and would be mitotically stable by the inheritance of the autoregulatory transcription factors themselves. In order to test for the potential of cellular levels of autoregulation transcription factors to specify differentiated cell types. I will design an artificial autoregulatory transcription factor that will have alternative steady state cellular levels. The autoregulatory transcription factor will consist of the gene encoding the yeast activator, GAL4, driven off a promoter containing two GAL4 binding sites. Each steady state cellular level of GAL4 will specify a unique epigenetic state that is phenotypically distinguishable by the activity of a reporter lacZ gene containing GAL4 binding sites in its promoter. The inheritance of the alternative epigenetic states in mitosis and meiosis will then be determined.
Keller, A D (1994) Specifying epigenetic states with autoregulatory transcription factors. J Theor Biol 170:175-81 |