The epigenetic regulation of RIZ1 in human leukemia
Beaton-Brown, Erika Lauren Dawn
Cancer has been thought of as a mostly genetic phenomenon, however recent research into epigenetic causes of cancer emphasizes that these causes of cancer are also important. RIZ1 is a tumor suppressor which is silenced in many human leukemias, such as human Acute Myeloid Leukemia and Chronic Myelogenous Leukemia. It was the goal of this thesis to re-express RIZ1 using three epigenetic drugs: decitabine, a DNA methylation inhibitor, Trichostatin A, a histone deacetylase inhibitor and chaetocin, an inhibitor of SUV39h1. Cells were treated with these drugs and analyzed for toxicity, methylation status, and RIZ1 expression levels. The synergy between the drugs was also determined. It was found that cells treated with decitabine and chaetocin had an induction of RIZ1 expression. Chaetocin induced RIZ1 expression without affecting the methylation status of the cell. Also, cells which were treated with decitabine paired with either Trichostatin A or chaetocin showed the highest amount of RIZ1 expression. Cells treated with all three drugs together had a higher amount of RIZ1 expression than cells treated with either drug alone, however had less expression than cells which had been treated with decitabine paired with either Trichostatin A or chaetocin. Using these data a model was developed in which H3K9 methylation is the dominant epigenetic event in transcriptional silencing.
DegreeMaster of Science (M.Sc.)
SupervisorGeyer, C. Ronald
CommitteeNazarali, Adil J.; Laferte, Suzanne; Khandelwal, Ramji L.; Roesler, William J.