The long-term goal of this work is to learn how mammalian cells produce levels of m-RNA appropriate to their specialized functions. This will be accomplished by investigating the roles of basal and activated transcription factors in setting m-RNA levels. The results will contribute to learning how mutant factors lead to inappropriate m-RNA production, a component of the imbalances that are associated with cancer.
The specific aims of this project are: 1. To learn the relationships among the critical ATP-dependent steps occurring at polymerase II promoters. These include start site DNA opening, polymerase phosphorylation and transcription initiation. 2. To learn what mechanistic features limit the ability to transcribe a polymerase II promoter. This includes learning the roles of specific factors and elements in setting both the rate and efficiency of transcription initiation and re-initiation. 3. To learn to what extent the principles discovered in aims l and 2 might be generally applicable. This includes comparing selected promoters, with emphasis on TATA versus initiator and basal versus activated.
| Tran, Khiem; Gralla, Jay D (2010) The TFIIB tip domain couples transcription initiation to events involved in RNA processing. J Biol Chem 285:39580-7 |
| Tran, Khiem; Gralla, Jay D (2008) Control of the timing of promoter escape and RNA catalysis by the transcription factor IIb fingertip. J Biol Chem 283:15665-71 |
| Wolner, B S; Gralla, J D (1997) Promoter activation via a cyclic AMP response element in vitro. J Biol Chem 272:32301-7 |
| Jiang, Y; Triezenberg, S J; Gralla, J D (1994) Defective transcriptional activation by diverse VP16 mutants associated with a common inability to form open promoter complexes. J Biol Chem 269:5505-8 |
| Chang, C; Gralla, J D (1994) A critical role for chromatin in mounting a synergistic transcriptional response to GAL4-VP16. Mol Cell Biol 14:5175-81 |
| Jiang, Y; Gralla, J D (1994) RNA polymerase II phosphorylation: uncoupling from GAL4-VP16 directed open complex formation and transcription in a reconstituted system. Nucleic Acids Res 22:4958-62 |
