| |

| 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 combine biochemical and structural approaches, including X-ray crystallography, in our studies of chromatin enzymes. The questions that we wish to address include:
|
| |
1. |
how chromatin enzymes and transcription factors recognize nucleosomes and, |
| |
2. |
how gene activity is regulated on a chromatin template. |
| 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 30th Summer Symposium in Molecular Biology on the topic of Chromatin and Epigenetic Regulation of Transcription was held on June 21-24, 2011. |
 |
| |
|
 |
Our research is supported by the National
Institutes of Health.
We gratefully acknowledge past support from the Pew
Scholars Program in the Biomedical Sciences. |
| |
|
| |
|
| Members of our Lab: |
Contact Info: |
| |
PI |
Song Tan |
468A North Frear Laboratory |
| |
Postdoctoral Fellows |
T.S. Girish |
University Park, PA 16802 |
| |
|
Rob McGinty |
(814) 865-3355 (office) |
| |
Research Associates |
Justin Malloy |
(814) 865-3354 (lab) |
| |
|
Allen Minns |
|
| |
Grad Students |
Jiehuan Huang |
|
| |
|
Matt Jennings |
|
| |
|
Sang A Kim |
|
| |
Undergraduates |
Elisabet Bjanes |
Josh McAnulty |
| |
|
Ryan Henrici |
Chris Steinman |
| |
|
Zach Hostetler |
Viktor Tollemar |
| |
|
|
|
| |
|
|
|
Selected Publications:
- Chittuluru, J.R., Y. Chaban, J. Monnet-Saksouk, M. J. Carrozza, V. Sapountzi, W. Selleck, J. Huang, M. Cramet, S. Allard, G. Cai1, J. L. Workman, M.J. Fried, S. Tan, J. Cote and F. J. Asturias (2011). Structure and nucleosome interaction of the NuA4 and Piccolo-NuA4 histone acetyltransferase complexes. Nature Str. Mol. Biol. , 39:8378-8391. (abstract)
- Chatterjee, N., D. Sinha, M. Lemma-Dechassa, S. Tan, M. A. Shogren-Knaak, B. Bartholomew (2011). Histone H3 tail acetylation modulates ATP-dependent remodeling through multiple mechanisms. Nucl. Acid Research, 39:8378-8391. (abstract)
- Charles, G.M., C. Chen, S. C. Shih, S. R. Collins, P. Beltrao, X. Zhang, T. Sharma, S. Tan, A. L. Burlingame, N. J. Krogan, H. D. Madhani, G. J. Narlikar (2011). Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress. PNAS, 108:10620-10625. (abstract)
- Tan, S. and C.A. Davey (2011) Nucleosome stuctural studies. Curr. Opin. Struct. Biol., 21:128-136. (abstract)
- Tan, S. and K. Nagai (2011) Diversity makes for a rich tapestry. Curr. Opin. Struct. Biol., 21:81-82.
- Makde, R.D., J.R. England, H. Yennawar and S. Tan (2010). Structure of RCC1 chromatin factor bound to the nucleosome core particle. Nature, 467:562-566. (abstract)
- England, J.R., J. Huang, M.J. Jennings, R. D. Makde, and S. Tan (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. (abstract)
- Choy, J.S., S. Wei, J.Y. Lee, S. Tan, S. Chu and T.H. Lee (2010) DNA methylation increases nucleosome compaction and rigidity, J. Am. Chem. Soc., 132:1782-1783. (abstract)
- Psathas, J.N., S. Zheng, S. Tan and J. Reese (2009) Set2-dependent K36 methylation is regulated by novel intratail interactions within H3, Mol. Cell. Biol., 29:6413-6426. (abstract)
- S. Tan and J. Reese (editors) (2009) BBA - Gene Regulatory Mechanisms Special Issue on Epigenetics, 1789:1-68.
- Selleck, W. and S. Tan (2008) Recombinant protein complex expression in E. coli, Curr Protocols Protein Sci, Chapter 5, unit 5.21. (abstract)
- Altaf, M., R.T. Utley, N. Lacoste, S. Tan, S.D. Briggs, J. Cote (2007) Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin, Mol. Cell, 28:1002-1014. (abstract)
- Barrios, A., W. Selleck, B. Hnatkovich, R. Kramer, D. Sermwittayawong 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., W. Selleck, S.J. McBryant, J.C. Hansen, S. Tan and J.M. Denu (2007) Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex, Biochemistry, 46:2091-2099. (abstract)
- Berndsen, C.E., B.N. Albaugh, S. Tan and J.M. Denu (2007) Catalytic mechanism of a MYST family histone acetyltransferase, Biochemistry, 46:623-629, Accelerated Publication. (abstract)
- Sermwittayawong, D. and S. Tan (2006) SAGA binds TBP via its Spt8 subunit in competition with DNA, implications for TBP recruitment, EMBO Journal, 25:3791-3800. (abstract)
- Doyon Y., C. Cayrou, M. Ullah, A.J. Landry, V. Cote, W. Selleck, W.S. Lane, S. Tan, W.J. Yang, X.J. and J. Cote (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., I. Fortin, D. Sermwittayawong, J. Cote and S. Tan (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., J.L. Malecki, H.D. Agnew, D.J. Michelson-Horowitz and S. Tan (2005) Comparison of Affinity Tags for Protein Purification, Prot. Expr. Purif., 41:98-105. (abstract)
- Tan, S., R.C. Kern and W. Selleck (2005) The pST44 polycistronic expression system for producing protein complexes in Escherichia coli, Prot. Expr. Purif., 40:385-395. (abstract)
- Doyon, Y., W. Selleck, W.S. Lane, S. Tan and J. Côté (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. , D. Cronier, W. Selleck, N. Lacoste, R.T. Utley, S. Allard, J. Savard, W.S. Lane, S. Tan and J. Côté (2003) Yeast Enhancer of polycomb defines global Esa1-dependent
acetylation of chromatin, Genes
& Dev, 17:1415-1428. (abstract)
- Bleichenbacher, M.M., S. Tan and T.J. Richmond (2003) Novel
Interactions Between the Components of Human and Yeast TFIIA/TBP/DNA
Complexes, J. Mol Biol.,
332:783-793. (abstract)
- Boyer, L.A., M.R. Langer, K.A. Crowley, S. Tan, J.M. Denu, and C.L. Peterson (2002) Essential role for the SANT domain
in the functioning of multiple chromatin remodeling enzymes. Mol.
Cell, 10:935-942. (abstract)
- Balasubramanian, R., M.G. Pray-Grant, W. Selleck, P.A. Grant
and S. Tan (2002) Role of the Ada2 and Ada3 transcriptional
coactivators in histone acetylation, J.
Biol. Chem., 277: 7989-7995. (abstract)
- Selleck, W., R. Howley, J. Fang, V. Podolny, M.G. Fried,
S. Buratowski and S. Tan (2001) A histone fold TAF octamer
within the yeast TFIID transcriptional coactivator, Nature
Struct. Biol., 8:695-700. (abstract)
- Brown, C.E., L. Howe, K. Sousa, S.C. Alley, M.J. Carrozza,
S. Tan and J.L. Workman (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., S. Tan and T.J. Richmond (2000) Novel
Dimerization Fold of RAP30/RAP74 in Human TFIIF at 1.7 Å
Resolution , J. Mol
Biol., 302: 1119-1127. (abstract)
- Tan, S., Y. Hunziker, L. Pellegrini and T.J. Richmond (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 T.J. Richmond (1998) Crystal structure
of the yeast MATalpha2/MCM1/DNA ternary complex, Nature,
391: 660-666. (abstract)
- Tan, S., Y. Hunziker, D.F. Sargent and T.J. Richmond
(1996) Crystal structure of a yeast TFIIA/TBP/DNA complex, Nature,
381: 127-134. (abstract)
- Pellegrini, L, S. Tan and T.J. Richmond (1995) Structure
of serum response factor core bound to DNA, Nature,
376: 490-498. (abstract)
|
|