The newly formed Chromatin and Gene Regulation Core provides state-of-the-art tools for analysis of gene expression, including alterations in chromatin structure, in the brain's reward regions in depression. Core services are utilized by all of the Center's five Projects, since these molecular tools have been validated not only for study of rodent tissue, but also for human brain tissue obtained at autopsy. The parallel analysis of brain reward regions in animal models of depression, and in human depressed patients, offers a particularly powerful translational dimension to our Center. All of the Center's Projects utilize DMAexpression arrays to study differences in mRNA levels within brain reward regions of experimental animals and humans. This has been expanded recently to include arrays for miRNAs (microRNAs), endogenous inhibitors of mRNA expression. The Core provides the arraying and array analysis for Project investigators. A major advance over the first 4 years of the Center has been the development of experimental protocols to study changes in chromatin structure within brain reward regions in rodent models and in human tissue. This includes chromatin immunoprecipitation (ChIP) assays as well as ChIP combined with DMA promoter microarrays, so-called """"""""ChIP on chip"""""""" assays. These exciting techniques are now being applied to Project studies as a major new initiative for our Center. By centralizing these activities into this new Core, we ensure a high quality of data and the ready ability to compare and contrast findings across the various Projects. Indeed, the array data already accumulated have demonstrated many common changes in gene expression in mice with mutations in the various genes of interest to the four preclinical Projects and in depressed human tissue. Economic savings are also achieved. We should mention that DNA expression array analyses were included in the Transgenic Core of our original Conte Center. However, given the expanded use of these arrays, expansion to analysis of miRNAs, and our new initiatives in chromatin remodeling, it makes sense to create this new Core, which supports highly cohesive studies of gene regulation. Together, the advanced technologies provided by this new Core offer an unprecedented evaluation of regulation of gene expression in brain reward regions in depression.
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