Song Tan
Professor of Biochemistry and Molecular Biology
468A North Frear LaboratoryUniversity Park, PA 16802
Research Interests
Structural biology of eukaryotic gene regulation
Research Summary
"Gene regulation is fundamental to the proper functioning of a cell, and many cancers can be traced to abnormal gene regulation. Our goal is to understand how genes are regulated by combining genetic, biochemical and structural descriptions. Our expectation is that such information will contribute to the development of future therapeutic agents against cancer and other human diseases.
We are particularly interested in how chromatin enzymes recognize and interact with the nucleosome. Despite the hundreds of chromatin enzymes discovered and characterized in vivo, we currently lack a molecular understanding of how these proteins bind to their physiological substrate, the nucleosome. To this end, we perform biochemical studies of chromatin enzymes and nucleosomes, and we use X-ray crystallography to determine their three-dimensional structures.
The two rate-limiting steps in structure determination of large complexes by X-ray crystallography are generating large quantities of high purity material and crystallizing the complexes. We have developed methods for reconstituting recombinant multicomponent complexes and we continue research to improve those methods. We are also investigating novel methods and tools for crystallizing multicomponent complexes.
For more information including pictures and movies of proteins and DNA, please visit our lab's web site.
| Crystal structure of the RCC1/nucleosome complex. | |
Production of recombinant protein complexes for crystallization by polycistronic expression |
Representative Publications
- Chittuluru J.R., Chaban Y., Monnet-Saksouk J., Carrozza, M.J., Sapountzi, V., Selleck, W. Huang, J., Utley, R.T., Cramet, M., Allard, S., Cai, G., Workman, J.L., Fried, M.G., Tan, S.,
Côté, J., Asturias, F.J. (2011) Structure and nucleosome interaction of the NuA4 and Piccolo-NuA4 histone acetyltransferase complexes. Nature Mol. Str. Biol., 18, 1196-1203.
- Tan, S. and Davey, C.A. (2011). Nucleosome structural studies. Curr Opin Struct Biol, 21, 128-136.
- Makde, R.D., England, J.R., Yennawar, H. and Tan. S. (2010). Structure of RCC1 chromatin factor bound to the nucleosome core particle. Nature, 467:562-566.
- England, J.R., Huang, J., Jennings, M.J., Makde, R.D., and Tan, S. (2010). RCC1 uses a conformationally diverse loop region to interact with the nucleosome: A model for the RCC1-nucleosome complex. J Mol Biol 398, 518-529.
- Choy, J.S., Wei, S., Lee, J.Y., Tan, S., Chu, S., and Lee, T.H. (2010). DNA methylation increases nucleosome compaction and rigidity. J Am Chem Soc 132, 1782-1783.
- Psathas, J.N., Zheng, S., Tan, S., and Reese, J.C. (2009). Set2-dependent K36 methylation is regulated by novel intratail interactions within H3. Mol Cell Biol 29, 6413-6426.
- Selleck, W. and S. Tan (2008) Recombinant protein complex expression in E. coli, Curr Protocols Protein Sci, Chapter 5, unit 5.21.
- Barrios, A., Selleck, W., Hnatkovich. B., Kramer, R., Sermwittayawong, D. and Tan, S. (2007) Expression and purification of recombinant yeast Ada2/Ada3/Gcn5 and Piccolo NuA4 histone acetyltransferase complexes, Methods, 41:271-277.
- Berndsen C.E., Selleck, W., McBryant, S.J., Hansen, J.C., Tan, S. and Denu, J.M. (2007) Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex, Biochemistry, 46:2091-2099.
- Berndsen, C.E., Albaugh, B.N., Tan, S. and Denu, J.M. (2007) Catalytic mechanism of a MYST family histone acetyltransferase,Biochemistry, 46:623-629. Accelerated Publication.
- Sermwittayawong, D. and Tan, S. (2006) SAGA binds TBP via its Spt8 subunit in competition with DNA: implications for TBP recruitment, EMBO J, 25:3791-3800.
