This project is focused on the identification and characterization of a yeast transcriptional coactivator, the ADA/GCN5 complex. Five subunits of this complex were identified in the prior granting period by a novel genetic screen. One of the subunits, GCN5, has histone acetyl transferase activity, suggesting a biochemical mechanism of action of this coactivator. In the next period the research will purify the coactivator complex to homogeneity and study its biochemical properties in detail. This will reveal the role of each individual subunit in the complex and provide mechanistic insight into coactivator function. Also, genetic screens will get at the target of this complex in the general transcriptional machinery and detail the architecture within the complex. Also, the biochemical function of the C-terminal domain of GCN5 will be investigated. This region, termed the bromo-domain, is found in many diverse kinds of coactivators and its mechanism of action will prove central to transcriptional activation. Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050207-07
Application #
6138477
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Tompkins, Laurie
Project Start
1994-01-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
7
Fiscal Year
2000
Total Cost
$204,172
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Horiuchi, J; Silverman, N; Pina, B et al. (1997) ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3. Mol Cell Biol 17:3220-8
Horiuchi, J; Silverman, N; Marcus, G A et al. (1995) ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Mol Cell Biol 15:1203-9
Marcus, G A; Silverman, N; Berger, S L et al. (1994) Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. EMBO J 13:4807-15