To understand how genes are regulated in a cell, we must learn how the cellular transcription machinery operates on DNA packaged as chromatin. The SAGA (Spt-Ada-Gcn5-acetyltransferase) and NuA4 (nucleosome acetyltransferase of histone H4) coactivator complexes control transcription from a chromatin-based template. In particular, both SAGA and NuA4 acetylate the histone tails of nucleosomes to loosen the chromatin structure and/or to recruit other chromatin enzymes.

Although Gcn5 is the catalytic subunit of the SAGA complex, it is only able to acetylate histones and it does so very inefficiently. To acetylate the physiologically relevant substrate, the nucleosome, Gcn5 requires additional SAGA subunits Ada2 and Ada3. Similarly, the Esa1 catalytic subunit of the NuA4 complex requires Epl1 and Yng2 to function efficiently on nucleosomes (Ep1l, Yng2 and Esa1 form the Piccolo NuA4 complex).

Despite the importance of chromatin enzymes, we still do not understand how they recognize their nucleosome substrate. To address this fundamental and important problem, several projects in our lab focus on biochemical and structural studies of the Ada3/Ada2/Gcn5 and Piccolo NuA4 subcomplexes that we identified with our collaborators. Our goal is to understand how these catalytic complexes bind to and then acetylate nucleosomes to activate transcription.

Pointers to articles in the popular press, podcasts and review articles about chromatin and chromatin modifications can be found in the background reading section.

References:

• 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)

• 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)
  
  
• 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)
  
  
• 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)
  

• 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)