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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH096890-03
Application #
8672683
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Labonté, Benoit; Engmann, Olivia; Purushothaman, Immanuel et al. (2017) Sex-specific transcriptional signatures in human depression. Nat Med 23:1102-1111
Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao et al. (2017) DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons. Nat Commun 8:14712
Nätt, Daniel; Barchiesi, Riccardo; Murad, Josef et al. (2017) Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain. Sci Rep 7:11082
Loh, Yong-Hwee Eddie; Feng, Jian; Nestler, Eric et al. (2017) Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification Landscapes in Mouse Brain Using ChlP-seq Data. Bio Protoc 7:
Peña, Catherine J; Kronman, Hope G; Walker, Deena M et al. (2017) Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science 356:1185-1188
Lopez, Juan Pablo; Fiori, Laura M; Cruceanu, Cristiana et al. (2017) MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nat Commun 8:15497
Jiang, C; Lin, W-J; Sadahiro, M et al. (2017) VGF function in depression and antidepressant efficacy. Mol Psychiatry :
Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacology 42:62-80
Brancato, Anna; Bregman, Dana; Ahn, H Francisica et al. (2017) Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens. Neuroscience 350:180-189
Feng, Jian; Pena, Catherine J; Purushothaman, Immanuel et al. (2017) Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Neuropsychopharmacology 42:1657-1669

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