The SWI/SNF chromatin remodeling complex uses the energy of ATP to alter nucleosomes to make DNA accessible to transcription machinery. Aberrations in chromatin remodeling can lead to development of cancer, such as loss of the SWI/SNF complex member BAF47 in rhabdoid tumors. BRG1, one of the catalytic subunits in human SWI/SNF complexes, is lost in ~30% of NSCLC cell lines. LOH surrounding the BRG1 loci at, 19p13.2, has been shown in human lung tumor tissue. Loss of BRG1/BRM expression was found in ~10% of human primary tumors and correlated with poor prognosis. Similarly, loss of E-cadherin (a metastasis suppressor and cellular adhesion molecule) expression was found in ~10% of NSCLC and correlated with dedifferentiation and decreased survival. Ecadherin is commonly silenced by promoter hypermethylation in NSCLC. We have performed chromatin immunoprecipitation to show BRG1 is at the promoter of E-cadherin in MCF7 cells that express high levels of E-cadherin. BRG1/BRM deficient cells examined by western blot were found to have significantly reduced levels of E-cadherin protein expression. Transfection of BRG1 into BRG1/BRM deficient cells induces reexpression of E-cadherin protein in a similar manner as treatment with 5-azacytidine. Therefore, loss of BRG1 expression may promote aberrant methylation of the E-cadherin promoter and subsequent silencing of the gene. We are currently screening H522 cells, a lung cancer cell line deficient for BRG1/BRM, for expression of other markers of lung cancer such as; p16 and FHIT. We will then check if transfection of BRG1, and treatment with 5-azacytidine are able to reexpress those markers. Bisulfite sequencing will be preformed to see if those markers promoters are demethylated upon transfection of BRG1, and treatment with 5-azacytidine. We will also do chromatin immunoprecipitation to see if BRG1 is present at those promoters. These experiments should help establish a role for BRG1 in maintaining methylation patterns of critical genes in normal lung tissue.