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Michael J. Pazin, Ph.D., Investigator Chromatin Structure and Function Unit Laboratory of Cellular and Molecular Biology Email: pazinm@grc.nia.nih.gov |
| Biography: Michael received his B.S. at M.I.T. in 1986, and his Ph.D. at the University of California San Francisco in 1992. He began working on chromatin as a postdoc at the University of California San Diego in 1997. Dr. Pazin was appointed Assistant Biologist at Massachusetts General Hospital and Assistant Professor at Harvard Medical School. He joined the NIA in 2004. |
| SWI/SNF Chromatin Remodelers Regulate T Cell Fates and Functions: Eukaryotic DNA is packaged into chromatin in the nuclei of eukaryotic cells. The basic repeated unit of chromatin is the nucleosome, shown at right (redrawn from Luger/Richmond). Chromatin was once viewed as a static barrier to nuclear processes, including transcription, replication, recombination and repair. Chromatin is now widely recognized as an important regulatory opportunity for nuclear processes. We are particularly interested in how chromatin structure changes, and how distal transcriptional regulatory elements function in the context of chromatin. The overall goal of our lab is to determine how changes in chromatin structure regulate gene expression. We are particularly interested in the role of the ATP-dependent remodeling enzyme SWI/SNF. We are trying to understand 1) the mechanisms of gene regulation by chromatin remodeling, 2) the role of different versions of the SWI/SNF complexes 3) how chromatin remodeling regulates cell fate and cell function. We use cell-based approaches to study these questions, focusing on T cells. |  |
| We are determining the role of remodeling enzymes in lymphocytes. We are examining the mechanism and target selection of ATP-dependent remodeling enzymes. We alter the function of targeted enzyme subunits and measure changes in gene expression using arrays and real-time PCR. We identify genes that are directly regulated by enzymes of interest using chromatin immunoprecipitation, and determine changes in chromatin structure. We examine the biological role of remodeling enzymes in lymphocytes. We have recently found that BRG1, a SWI/SNF component, is dynamically recruited to the Th2 LCR. Recruitment depends upon specfic transcription factors. The LCR chromatin structure is dynamic, and dependent upon BRG1. |
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