Song Tan Associate Professor of Biochemistry and Molecular Biology Center for Gene Regulation 468A North Frear Laboratory, University Park, PA 16802 Phone: (814) 865-3355 Fax: (814) 863-7024 Email: sxt30@psu.edu B.S. in physics, Cornell University Ph.D. in molecular biology, University of Cambridge Post-doctoral work in structural biology, ETH-Zürich Tan Lab Web Site Member of Center for Eukaryotic Gene Regulation

Structural Biology of Eukaryotic Gene Regulation

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 dissecting the molecular mechanisms of transcription on a chromatin template to understand how genes are turned off and on. To do so, we perform biochemical studies of chromatin enzymes and we use X-ray crystallography to determine their three-dimensional structures. The questions that we wish to address include:

1. how chromatin enzymes and transcription factors recognize nucleosomes and,

2. how coactivators enhance transcription by recruiting the TBP general transcription factor to the promoter.

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.

Representative Publications

• 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.
• Doyon Y., Cayrou, C., Ullah, M., Landry, A.J., Cote, V., Selleck, W., Lane, W.S., Tan, S. , Yang, X.J. and Cote, J. (2006) ING Tumor Suppressor Proteins Are Critical Regulators of Chromatin Acetylation Required for Genome Expression and Perpetuation, Mol. Cell, 21:51-64.
• Selleck, W., Fortin, I., Sermwittayawong, D., Cote, J. and Tan, S. (2005) The yeast Piccolo NuA4 HAT complex requires the Enhancer of Polycomb A and chromo domains to acetylate nucleosomes, Mol. Cell. Biol., 25:5535-5542.
• Lichty, J.L., Malecki, J.L., Agnew, H.D., Michelson-Horowitz, D.J. and Tan, S. (2005) Comparison of Affinity Tags for Protein Purification, Prot. Expr. Purif., 41:98-105.
• Tan, S. , Kern, R.C. and Selleck, W. (2005) The pST44 polycistronic expression system for producing protein complexes in Escherichia coli, Prot. Expr. Purif., 40:385-395.
• Doyon, Y., Selleck, W., Lane, W.S., Tan, S. and Côté, J. (2004) Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to human, Mol. Cell. Biol., 17:1415-1428.
• Boudreault, A.A. , Cronier, D., Selleck, W., Lacoste, N., Utley, R.T., Allard, S., Savard, J., Lane, W.S., Tan, S. and Côté, J. (2003) Yeast Enhancer of polycomb defines global Esa1-dependent acetylation of chromatin, Genes & Dev, 17:1415-1428.
• Boyer, L.A., Langer, M.R., Crowley, K.A., Tan, S., Denu, J.M., and Peterson, C.L. (2002) Essential role for the SANT domain in the functioning of multiple chromatin remodeling enzymes. Mol. Cell, 10:935-942.
• Balasubramanian, R., Pray-Grant, M.G., Selleck, W., Grant, P.A. and Tan, S. (2002) Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation, J. Biol. Chem., 277: 7989-7995.
• Selleck, W., Howley, R., Fang, J., Podolny, V., Fried, M.G., Buratowski, S. and Tan, S. (2001) A histone fold TAF octamer within the yeast TFIID transcriptional coactivator, Nature Struct. Biol., 8:695-700.
• Brown, C.E., Howe, L, Sousa, K., Alley, S.C., Carrozza, M.J., Tan, S. and Workman, J.L. (2001) Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit, Science, 292: 2333-2337.
• Tan, S. (2001) A Modular Polycistronic Expression System for Overexpressing Protein Complexes in Escherichia coli, Prot. Expr. Purif., 21:224-234.
• Tan, S., Hunziker, Y., Pellegrini,L. and Richmond, T.J. (2000) Crystallization of the yeast MATalpha2/MCM1/DNA ternary complex: general methods and principles for protein/DNA cocrystallization, J. Mol. Biol., 297: 947-959.
• Tan, S. and Richmond, T.J. (1998) Crystal structure of the yeast MATalpha2/MCM1/DNA ternary complex, Nature, 391: 660-666.
• Tan, S., Hunziker, Y., Sargent, D.F. and Richmond, T.J. (1996) Crystal structure of a yeast TFIIA/TBP/DNA complex, Nature, 381: 127-134.

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