The main objective of the Chromatin and Gene Analysis Core is to provide the technical and bioinformatic infrastructure to optimally mine the vast amounts of genome-wide gene expression and chromatin data that will be generated from the Center's work. Center investigators have lead the field in several aspects of genome-wide chromatin analyses, including pioneering these approaches in brain, which offers several unique technical challenges. Together, we have defined optimal methods of chromatin immunoprecipitation (ChlP) for mouse and human brain. As well, this Core has established expertise in analyzing the rich ChlP- Seq and RNA-Seq datasets obtained, and will work to continually improve the tools available. Much of the genome-wide data obtained by our Center will be generated by the individual Projects and analyzed by the Core. In parallel, the Core will run more routine genome-wide assays on defined animal models and thereby provide a foundation for the more specific and sophisticated measures in the individual Projects. This will include screening families of chromatin regulatory proteins for alterations in mouse depression models, which will drive research in the individual Projects. Additionally, the Core will pilot several novel technologies and approaches, including testing whether any potent trans-generational transmission of behavioral abnormalities can be mediated via sperm or ova from stressed mice. All four Projects will be served by this Core;Projects 1-3 for the analysis of animal models and Project 4 for postmortem human brain tissue, which offers an additional set of unique technical challenges. By consolidating the analytical work and some routine genome-wide analyses within a centralized Core, we ensure rigorous control over the data and facilitate comparisons of experimental findings across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of our analytical expertise. The Core is also responsible, with the Administrative Core, in developing and maintaining the multiple ways in which these highly complex and large datasets, and analytical tools, are both shared across the multiple Projects and laboratories that comprise the Center as well as shared with the scientific community and lay public at large.
Depression has a lifetime risk of ~15% for the U.S. general population, yet available antidepressant therapies are based on serendipitous discoveries over 6 decades ago, and fully treat <50% of all affected individuals. An improved understanding of the molecular basis of depression will lead to improved treatments and diagnostic tests-a high priority for the National Institutes of Health.
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| Zhang, Song; Zhang, Hongxing; Ku, Stacy M et al. (2018) Sex Differences in the Neuroadaptations of Reward-related Circuits in Response to Subchronic Variable Stress. Neuroscience 376:108-116 |
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