In this renewal application, the applicant proposes to continue efforts to unravel the mechanisms by which viral transactivators and the cellular transcription apparatus interact with each other to regulate gene expression. In particular, a significant effort will be devoted to isolating, cloning and characterizing members of a novel class of transcription factors called TAFs/coactivators which are responsible for mediating regulation by enhancer binding proteins. The applicant hopes to develop in vitro and in vivo assays to dissect the function of independent TAFs as well as the TBP/TAF complex. One intriguing and important objective is to search for putative cell-type specific TAFs. A significant effort will also be directed at interactions between the viral oncogene, T antigen, tumor suppressors (p53) and components of the transcription machinery. A major new area of investigation will be the development of reconstituted transcription reactions designed to evaluate the individual steps along the transcription cycle that may be subject to regulation by specific viral and cellular factors. Finally, the applicant hopes to begin high resolution structural analysis of various protein:protein interfaces that form the basis of activator:coactivator interactions. In particular, he will employ a battery of biochemical and physical methods to determine the 3D structure of activation domains and to test various hypotheses concerning the dynamic process of transcription factor interplay.
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| Zhou, Haiying; Kaplan, Tommy; Li, Yan et al. (2013) Dual functions of TAF7L in adipocyte differentiation. Elife 2:e00170 |
| Guglielmi, Benjamin; La Rochelle, Natalie; Tjian, Robert (2013) Gene-specific transcriptional mechanisms at the histone gene cluster revealed by single-cell imaging. Mol Cell 51:480-92 |
| Fong, Yick W; Cattoglio, Claudia; Tjian, Robert (2013) The intertwined roles of transcription and repair proteins. Mol Cell 52:291-302 |
| Revyakin, Andrey; Zhang, Zhengjian; Coleman, Robert A et al. (2012) Transcription initiation by human RNA polymerase II visualized at single-molecule resolution. Genes Dev 26:1691-702 |
| Fong, Yick W; Cattoglio, Claudia; Yamaguchi, Teppei et al. (2012) Transcriptional regulation by coactivators in embryonic stem cells. Trends Cell Biol 22:292-8 |
| Yao, Jie; Fetter, Richard D; Hu, Ping et al. (2011) Subnuclear segregation of genes and core promoter factors in myogenesis. Genes Dev 25:569-80 |
| D'Alessio, Joseph A; Ng, Raymond; Willenbring, Holger et al. (2011) Core promoter recognition complex changes accompany liver development. Proc Natl Acad Sci U S A 108:3906-11 |
| Liu, Zhe; Scannell, Devin R; Eisen, Michael B et al. (2011) Control of embryonic stem cell lineage commitment by core promoter factor, TAF3. Cell 146:720-31 |
| Fong, Yick W; Inouye, Carla; Yamaguchi, Teppei et al. (2011) A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell 147:120-31 |
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