The aim of the proposed research is to understand, in molecular terms, the mechanisms of the transcriptional and translational controls that operate during the heat shock response in Drosophila. From this understanding, we hope to be able to formulate a general model for the control of eucaryotic gene expression. First, we will identify the sequences in the DNA that are responsible for the transcriptional control of the expression of the heat shock genes, both in response to heat shock and in response to normal developmental signals, since subsets of the heat shock genes have been shown to be active at specific developmental stages. This will allow us to understand how and where the information necessary for the control of the transcription of eucaryotic genes is positioned on the DNA. We will then identify and isolate regulatory factors that interact with these sequences thereby modulating the transcription of these genes. We will study the cellular and chromosomal distribution of these factors under heat shock and non heat shock conditions, their interaction in vitro with the regulatory sequences on the DNA, and how alterations in these sequences affect both the in vitro interaction and the in vivo expression of these genes. Finally, we will study the structure of these genes at the chromatin level in order to understand the relationship between chromatin conformation at specific regions and inducibility and transcriptional activity of these genes. These studies, taken together, will allow us to understand in more detail not only how gene expression is controlled in eucaryotic organisms (a necessary first step toward understanding more complicated processes such as differentiation and carcinogenesis) but will also contribute to our knowledge of a very important and general physiological mechanism of defense of the cell against stress conditions commonly referred to as """"""""the heat shock response"""""""".
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