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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. in chemistry at M.I.T. in 1986, and his Ph.D. in cell biology at the University of California San Francisco in 1992. He began working on chromatin as a postdoctoral researcher with Dr. Jim Kadonaga 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 in the Department of Dermatology, where he continued to work on chromatin. He joined the NIA in 2004. |
| The Role of Chromatin Remodeling in Gene Regulation: 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 mechanistic barrier to nuclear processes, including transcription, replication, recombination and repair. Chromatin is now widely recognized as an important regulatory opportunity for nuclear processes. The overall goal of our unit is to determine how changes in chromatin structure regulate gene expression. We are particularly interested in the role of ATP-dependent remodeling enzymes, such as ACF, SWI/SNF, and Mi2. We are trying to understand 1) the mechanisms of chromatin remodeling, 2) the differences between remodeling enzymes, and 3) the biological role of chromatin in gene regulation. We use both cell-based and cell-free approaches to study these questions. |  |
| Cell-based Analysis of Chromatin Remodeling Enzyme Function: 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 also examine the biological role of remodeling enzymes in lymphocytes. |
| Cell-free (Biochemical) Analysis of Chromatin Remodeling Enzyme Mechanism: We are determining remodeling enzyme mechanisms using chromatin (arrays of nucleosomes) assembled with defined components. We measure changes in chromatin structure catalyzed by remodeling enzymes and programmed by transcription factors. We measure transcription using chromatin templates. Proteins are expressed in insect cells and bacteria, and purified using affinity and conventional chromatography. |
| Position Available: Postdoctoral position examining the role of chromatin remodeling in gene regulation. Experience with chromatin immunoprecipitation, biochemical assays with purified proteins or lymphocyte culture is desired. Contact Mike Pazin at pazinm@grc.nia.nih.gov. |
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