| The retinal transcription factor Nrl belongs to a distinct subfamily of basic motif leucine zipper (bZIP) DNA binding proteins. It binds to sequences in the rhodopsin promoter and activates transcription. Both over and under expression of rhodopsin has been implicated in inherited eye disease. To understand the regulation of Nrl, a human retinoblastoma cell line, Y79, was used as the model system. The objectives of this project were as follows: (1) to characterize the expression of Nrl in cultures of serum-starved Y79 cells after the addition of serum; (2) to determine the stability of Nrl when serum is withdrawn from proliferating Y79 cells; and (3) to identify if any growth or trophic factor known to induce gene transcription in vitro could induce the expression of Nrl in serum-starved Y79 cells. It was found that (1) Nrl expression is induced after 4h by the addition of serum to Y79 cells; (2) Nrl expression begins to decay 4h after serum is withdrawn from the culture medium; and (3) fibroblast growth factor 2, insulin-like growth factor 1 and 2, nerve growth factor, insulin and retinoids were each able to induce Nrl expression in Y79 cells after 24 hours. These agents are key players in retinal development. The finding that these factors induce Nrl expression could lead to insights into metabolic pathways that maintain photoreceptor function or are involved in photoreceptor cell death and eye disease. |
