Date of Award
Insulin-like growth factor-binding proteins, Growth hormone releasing factor, Genetic transcription -- Research, Gene expression -- Technique
The growth hormone (GH) and insulin-like factor 1 (IGF-1) growth axis is integral to growth, metabolism and tissue repair. This pathway involves binding of GH to the GH receptor and activation of the transcription factor, Stat5b, leading to nuclear transclocation, interaction with DNA binding sites in chromatin and stimulation of IGF-1 transcription. Stat5b binding sites have been determined experimentally by previous research but are all found far from the IGF-1 promoters and the mechanism by which Stat5b binding initiates IGF-1 gene transcription is currently unknown. Since no system for studying this process currently exists, the goal of this project is to create a cell-based transcriptional test system by placing the rat IGF-1 locus in the form of a linearized bacterial artificial chromosome (BAC) into mammalian cell line. The transgene then will be studied for GH regulation, Stat5b binding to specific DNA sequences, and the long distance interactions between Stat5b binding sites and the IGF-1 gene promoters that are for activating IGF-1 gene transcription. If successful, this project will help to answer fundamental questions about the GH IGF-1 growth axis, more specifically the role of Stat5b.
Morrison, Tiffany, "The Regulation of Insulin-like Growth Factor 1 by Growth Hormone via Stat5b" (2012). University Honors Theses. Paper 14.