Research accomplishments ? ? 1. We have further extended our knowledge of the estrogen receptor MTA3 Snail genetic pathway in the context of breast cancer. We have determined that exogenous expression of Snail in ER positive cell lines leads to loss of expression of ER itself. Chromatin immunoprecipitation experiments indicate that Snail directly associates with regulatory DNA at the ESR1 locus leading to repression, but not stable silencing, of ER expression. ? 2. We have determined that MTA3 serves as a useful marker in diagnosis of lymphomas. The protein is expressed at high levels in lymphomas of germinal center or post-germinal center origin. High level expression of MTA3 strongly predicts a germinal center pattern of gene expression.? 3. We collaborated with Dr. Xiaodong Cheng of Emory University to determine the crystal structure of the SANT domain of the ISWI protein from Xenopus laevis.? 4. We determined that expression of the transcription factor Snail in cells derived from neural crest is dependent on a novel enhancer located 3 of the coding sequence. In cells of this origin expressing Snail, we observed a long range contact between this enhancer element and the core promoter.
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