Mechanisms of epigenetic silencing of the c21 gene in Y1 adrenocortical tumor cells

We utilized Y1 adrenocortical carcinoma cell line as a model system to diss ect the events regulating epigenomic gene silencing in tumor cells. We show here that the chromatin structure of c21 gene is inactive in Y1 cells and that it could be reconfigured to an active form by either expressing antise nse mRNA to DNA methyltransferase 1 (dnmt1) or an attenuator of Ras protoon cogenic signaling hGAP. Surprisingly however, the known inducer of active c hromatin structure the histone deacetylase inhibitor trichostatin A TSA fai ls to induce expression of c21. These results suggest that the primary caus e of c21 gene silencing is independent of histone deacetylation. We present a model to explain the possible roles of the different components of the e pigenome and the DNA methylation and demethylation machineries in silencing c21 gene expression.