Gene regulation in cells requires the concerted action of gene specific activator and repressor proteins, general transcription factors, and chromatin modifying enzymes. These enzymes include the histone acetyltransferase multiprotein enzyme complexes which post-translationally acetylate the tails of histone protein components of chromatin. Since gene activity is well correlated with local histone acetylation in the cell, histone acetyltransferase complexes are likely to act as important coregulators of gene activity. The recent findings that such complexes also contain adaptor or coactivator proteins strengthened this relationship between histone acetylation and gene activation, and suggested that chromatin modifications and coactivator functions, such as recruitment to promoter regions, are coordinated processes. These activities may be involved in the development of human cancers since some of these coactivator proteins associate with cellular oncoproteins and tumor suppressor gene products. The long-term objectives of this proposal are to combine high-resolution structural descriptions with genetic and biochemical information to understand how eukaryotic gene regulatory complexes function. This proposal focuses on subcomplexes responsible for crucial functions of the yeast SAGA histone acetyltransferase complex. The primary goals include 1. analyzing the structure and function of the Ada2/Ada3/Gcn5 complex by biochemical methods, 2. determining the three-dimensional structure of the Ada2/Ada3/Gcn5 ternary complex by X-ray crystallography, 3. characterizing and crystallizing SAGA components bound to transcriptional activators and 4. characterizing and crystallizing SAGA components bound to general transcription factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060489-03
Application #
6520142
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Lewis, Catherine D
Project Start
2000-03-01
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
3
Fiscal Year
2002
Total Cost
$231,847
Indirect Cost
Name
Pennsylvania State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Jennings, Matthew J; Barrios, Adam F; Tan, Song (2016) Elimination of truncated recombinant protein expressed in Escherichia coli by removing cryptic translation initiation site. Protein Expr Purif 121:17-21
McGinty, Robert K; Tan, Song (2015) Nucleosome structure and function. Chem Rev 115:2255-73
McGinty, Robert K; Henrici, Ryan C; Tan, Song (2014) Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514:591-6
Lalonde, Marie-Eve; Avvakumov, Nikita; Glass, Karen C et al. (2013) Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev 27:2009-24
Huang, Jiehuan; Tan, Song (2013) Piccolo NuA4-catalyzed acetylation of nucleosomal histones: critical roles of an Esa1 Tudor/chromo barrel loop and an Epl1 enhancer of polycomb A (EPcA) basic region. Mol Cell Biol 33:159-69
Tan, Song (2012) Deciphering how the chromatin factor RCC1 recognizes the nucleosome: the importance of individuals in the scientific discovery process. Biochem Soc Trans 40:351-6
Chatterjee, Nilanjana; Sinha, Divya; Lemma-Dechassa, Mekonnen et al. (2011) Histone H3 tail acetylation modulates ATP-dependent remodeling through multiple mechanisms. Nucleic Acids Res 39:8378-91
Charles, Georgette M; Chen, Changbin; Shih, Susan C et al. (2011) Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress. Proc Natl Acad Sci U S A 108:10620-5
Chittuluru, Johnathan R; Chaban, Yuriy; Monnet-Saksouk, Julie et al. (2011) Structure and nucleosome interaction of the yeast NuA4 and Piccolo-NuA4 histone acetyltransferase complexes. Nat Struct Mol Biol 18:1196-203
Tan, Song; Davey, Curt A (2011) Nucleosome structural studies. Curr Opin Struct Biol 21:128-36

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