| Laboratory of Cellular and Molecular Biology |
Intramural Program Investigators ^ Home ^ |
| Michael J. Pazin, Ph.D., Investigator Chromatin Structure and Function Unit |
 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.Research Interests: Chromatin plays a critical role in regulating access to the information contained in the genome, as well as packaging the genome to allow it to fit within the nucleus of a cell. Chromatin structure can change rapidly when chromatin remodeling enzymes are recruited, yet can also apparently be a stable source of epigenetic memory. We are interested in how remodeling enzymes change chromatin structure, how they find their target sites, and how remodeling causes changes in gene expression. We focus on the ATP-dependent class of remodeling enzymes. We use cell-based and cell-free assays to examine this problem, using lymphocytes, neuronal cells and their genes as model systems. |
| T Cell Activation and Differentiation: Activated T cells express a number of transcription factors and cytokines, and the gene expression program changes when T cells differentiate. We are using T cell activation and T cell differentiation as model systems to investigate the function of ATP-dependent remodeling enzymes. We are asking what remodeling enzymes are required for gene expression, and measuring how they change the chromatin structure of their target loci. We use primary murine T cells as well as human and mouse T cell lines in these studies. We have identified a number of genes regulated by remodeling enzymes as well as binding sites for these enzymes in their target loci. |
| B Cells and Immunoglobulin Heavy Chain Regulation: Regulation of immunoglobulin loci is a complex process involving transcriptional regulation as well as gene rearrangement. It is believed that one important level of control is the accessibility of the loci, and that this may be regulated through chromatin structure. In collaboration with Ranjan Sen, we are using a cell-free system to determine how chromatin remodeling regulates transcription and recombination. We have identified transcription factors and remodeling enzymes that regulate chromatin structure. Remarkably, we have found a remodeling event that erases a DNase I hypersensitive site without reverting the chromatin structure to the ground state; furthermore, the transcription factor that initiates formation of the hypersensitivity is not displaced. We believe remodeling plays a causal role in transcription in this system, as the structural changes precede and correlate with changes in gene regulation. Moreover, remodeling occurs in the absence of transcription, while transcription is impaired in the absence of remodeling. |
| Neurons, Gene Expression and Differentiation: Neuronal cells undergo changes in gene expression during embryogenesis and differentiation, as well as during pathological processes such as Alzheimer's and Huntington's diseases. We are interested in how remodeling plays a role in regulating these gene expression programs. In collaboration with Mark Mattson, we are examining the chromatin structure of developmentally regulated genes. |
| Contact Information: Laboratory of Cellular and Molecular Biology Biomedical Research Center, room 06C220 251 Bayview Boulevard, Suite 100 Baltimore, MD 21224-6825 Phone 410-558-8094 Fax 410-558-8386 E mail pazinm@grc.nia.nih.gov For more information about the Laboratory: http://www.grc.nia.nih.gov/branches/lbc/lbc.htm |
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