Constitutive and inducible regulation of apolipoprotein CIII expression
This dissertation describes a group of experiments which define the function of two sequence elements in the apolipoprotein CIII gene promoter: C3P and N1. The C3P element is a positive regulatory transcriptional element which binds a liver enriched nuclear factor AF-1. The N1 element binds a hepatic factor whose identity and function are unknown. I used electrophoretic gel mobility shift assays, transient transfection assays, in vitro transcription experiments, and in vivo mouse studies to examine the function of these two sequence elements. I found that AF-1 can bind to the C3P element and activate the transcription of the apo CIII promoter; I also defined the nucleotides responsible for AF-1 binding and transcriptional activation in hepatocytes. The N1 element is bifunctional and depending upon the surrounding sequences, can either stimulate or repress the transcription of apo CIII in response to cellular signals. In addition, other elements appear to interact with the N1 element to repress the transcription of apo CIII. I identified the protein NF-$\kappa$B to be one of a number of hepatic proteins that can bind to the N1 element. I also demonstrate that CIII expression in mice is repressed in response to the same signals which repress the transcription of apo CIII in vitro. These data show that apo CIII transcription is transiently regulated in response to cellular signals and suggests that these signals are important in the regulation of lipid metabolism.
Gruber, Peter John, "Constitutive and inducible regulation of apolipoprotein CIII expression" (1992). Dissertations available from ProQuest. AAI9308582.