Project Summary

David J. Sweatt, Ph.D. (Distinguished Investigator 2007) of University of Alabama at Birmingham, aims to study the role of epigenetic alterations, such as chemical modifications to the chromatin structure or to DNA, and their relationship to behavior. The marking of DNA with methyl groups on cytosines or with modifications of chromatin-associated proteins allow for stable maintenance of gene expression in cells, including, now, in neuronal cells. Recently, Dr. Sweatt and others have found a role for the regulation of chromatin structure, through histone post-translational modifications, in long-term synaptic plasticity and long-term memory formation. These findings show that epigenetic mechanisms are part of a universal molecular alphabet for triggering long-lasting modifications at the molecular, cellular, and behavioral levels. More recently, he discovered that another epigenetic mechanism, DNA methylation, also is a dynamic process involved in controlling long-lasting changes in synaptic strength. These results, along with recent results from others, suggest a paradigm shift in scientific thinking about DNA methylation. As opposed to being a static mechanism set up during development as a permanent change, DNA methylation appears to be subject to ongoing regulation in the adult nervous system, subject to control by environmental influences. In this proposal, Dr. Sweatt will study methylation in certain brain-specific genes because of their role in synaptic plasticity, long-term behavioral change, schizophrenia and depression. He also will study methylation in neuronal tissue of animals subjected to fear conditioning and parental neglect and abuse because these models are useful for the study of mental illness.

Program Area: MULTIPLE FOCUS\Mood Disorders/Schizophrenia

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