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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:
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how chromatin enzymes and transcription factors recognize nucleosomes and, |
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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. |
| The Penn State 26th Summer Symposium in Molecular Biology on the topic of Chromatin and Epigenetic Regulation of Transcription was held on June 19-22, 2007. |
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Congratulations to Andrew Fleischman on his Penn State 2008 Undergraduate Summer Discovery Grant!
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Our research is supported by the National
Institutes of Health.
We gratefully acknowledge past support from the Pew
Scholars Program in the Biomedical Sciences. |
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| Members of our Lab: |
Contact Info: |
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PI |
Song Tan |
306 Althouse Laboratory |
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Postdoctoral Fellow |
Ravindra Makde |
University Park, PA 16802 |
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Research Associate |
Mike Porzio |
(814) 865-3355 (office) |
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Grad Students |
Jiehuan Huang |
(814) 865-3354 (lab) |
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Tom Koerber |
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Chris Valasek |
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Undergraduates |
Jason Aynardi |
Trusha Patel |
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Omkar Bhat |
Wil Santivasi |
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Joe England |
Adam Seitz |
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Andrew Fleischman |
Steve Tucker |
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Nathan Hazi |
Mei Zhou |
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Will Herbick |
Tom Zikos |
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Aaron Nogan |
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Selected Publications:
- Barrios, A., Selleck, W., Hnatkovich. B., Kramer, R., Sermwittayawong, D. and S. Tan (2007) Expression and purification of recombinant yeast Ada2/Ada3/Gcn5 and Piccolo NuA4 histone acetyltransferase complexes, Methods, 41:271-277. (abstract)
- Berndsen, C.E., Selleck, W., McBryant, S.J., Hansen, J.C. , S. Tan and J.M. Denu (2007) Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex, Biochemistry, 46:2091-2099. (abstract)
- Berndsen, C.E., Albaugh, B.N., Tan, S. and J.M. Denu (2007) Catalytic mechanism of a MYST family histone acetyltransferase, Biochemistry, 46:623-629, Accelerated Publication. (abstract)
- Sermwittayawong, D. and Tan, S. (2006) SAGA binds TBP via its Spt8 subunit in competition with DNA, implications for TBP recruitment, EMBO Journal, 25:3791-3800. (abstract)
- 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. (abstract)
- 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. (abstract)
- 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. (abstract)
- 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. (abstract)
- 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., 24:1884-1896. (abstract)
- 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. (abstract)
- Bleichenbacher, M.M., Tan, S. and Richmond, T.J. (2003) Novel
Interactions Between the Components of Human and Yeast TFIIA/TBP/DNA
Complexes, J. Mol Biol.,
332:783-793. (abstract)
- 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. (abstract)
- 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. (abstract)
- 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. (abstract)
- 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.
(abstract)
- Tan, S. (2001) A Modular Polycistronic Expression System
for Overexpressing Protein Complexes in Escherichia Coli, Prot.
Expr. Purif., 21: 224-234. (abstract)
- Gaiser, F., Tan, S. and Richmond, T.J. (2000) Novel
Dimerization Fold of RAP30/RAP74 in Human TFIIF at 1.7 Å
Resolution , J. Mol
Biol., 302: 1119-1127. (abstract)
- 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. (reprint)
- Tan, S. and Richmond, T.J. (1998) Crystal structure
of the yeast MATalpha2/MCM1/DNA ternary complex, Nature,
391: 660-666. (abstract)
- 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. (abstract)
- Pellegrini, L, Tan, S. and Richmond, T.J. (1995) Structure
of serum response factor core bound to DNA, Nature,
376: 490-498. (abstract)
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