Elucidation of ZEB-1 expression by identification of promoter regulatory elements

BIOL 44

Bynthia M. Anose, b-anose@bethel.edu and Kara Benjamin. Department of Chemistry and Biochemistry, Bethel University, 3900 Bethel Drive, St. Paul, MN 55112
The human Zinc finger E-box Binding Protein-1 (ZEB-1) is a highly conserved transcription factor with important functions in processes as diverse as myogenesis, hematopoiesis, and skeletal patterning. ZEB-1 belongs to a family of zinc-finger homeodomain proteins involved in essential developmental events related to epithelial to mesenchymal transitions (EMT). Previous research has identified ZEB-1 as a putative biomarker for the onset of metastasis in prostate cancer. Because it competes with other E-box binding proteins for regulatory elements, the precise levels of ZEB-1 are critical with respect to its downstream effects in normal tissues and probably in pathological situations such as cancer. However, the factors that regulate its gene expression and the signaling pathways in which ZEB-1 participates are largely unknown. In order to address these deficiencies, we began characterizing the human ZEB-1 gene regulatory elements. Based on these characterizations, a number of putative regulatory elements were identified. The data herein demonstrate that the expression of ZEB-1 is induced by several of these factors, including dihydrotestosterone (DHT) and its metabolic breakdown products.