A fundamental problem in biology is to understand the ways in which different cell types are regulated to express particular sets of genes during development. Although there are many levels at which gene expression may be modulated, transcriptional control is clearly of central importance. Since the DNA in eukaryotes is assembled as chromatin, it is of interest to determine the ways in which various aspects of chromatin structure may contribute to the transcriptional potential of a given gene. I plan to approach this question by studying the set of liver specific estrogen responsive chicken genes, in particular the three vitellogenin genes. Since the transcription of these genes can be experimentally modulated in both male and female liver cells by the addition of exogenous estrogen (even though male liver cells would never express these genes during normal development), it will be possible to describe the chromatin structures of these genes prior to, during, and following their transcriptional activation in vivo. In addition, by cloning these genes, making recombinant DNA constructions and introducing these chimeric genes back into primary cultures of liver cells (as well as oviduct cells, where the endogenous vitellogenin genes are not expressed despite the presence of functional estrogen receptors), it will be possible to identify regions of DNA that are required for the tissue specific transcriptional regulation of these genes by estrogen. In this way it should be possible to elucidate molecular details relevant to the tissue specific expression of these genes and to clarify the role that chromatin structure plays in this regulation.
