Research Summary
Mechanisms of transcriptional regulation in mammalian cells
Transcription is at the heart of gene expression and is subject to strict control. How transcriptional regulators function is the focus of research in this laboratory. Our studies concern two major project areas;
1. Regulation of the general transcription machinery
We are studying the mechanisms by which activator proteins stimulate transcription in mammalian cells. This involves both a biochemical approach and the use of in vivo transcription systems. A crucial function of transcriptional activators is the recruitment of the general transcription factor TFIIB to the promoter and is the subject of research in our laboratory.
2. Transcriptional regulation by the Wilms' tumor suppressor protein WT1
The transcriptional regulator WT1 is mutated in the pediatric cancer Wilms' tumor, and has also been linked with other malignancies including Leukemia. The mechanism of action of WT1 is complex, having both transcriptional activation and repression activities. We are engaged in dissecting the transcription function of WT1 both in vivo and in vitro. This includes the characterization of proteins that interact with WT1 to mediate its diverse transcription functions and how this is affected by mutation of WT1 in cancer.
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Selected Publications
- Deng, W., Malecová, B., Oelgeschläger, T. and Roberts, S.G.E. (2009). TFIIB recognition elements control the TFIIA-NC2 axis in transcriptional regulation. Molecular and Cellular Biology. 29, 1389-1400.
- Green, L.M., Wagner, K.J., Campbell, H.A., Addison, K. and Roberts, S.G.E. (2009). Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiation. Nucleic Acids Research 37, 431-440.
- Deng, W. and Roberts, S.G.E. (2007). TFIIB and the regulation of transcription by RNA polymerase II. Chromosoma 116, 417-429.
- Elsby, L.M., O’Donnell, A.J.M., Green, L.M., Sharrocks, A.D. and Roberts S.G.E. (2006). Assembly of TFIIB at a promoter in vivo requires contact with RNA polymerase II. EMBO Reports 7, 898-903.
- Deng, W. and Roberts, S.G.E. (2005). A core promoter element downstream of the TATA box that is recognized by TFIIB. Genes and Development 19, 2418-2423.
- Roberts, S.G.E. (2005). Transcriptional regulation by WT1 in development. Current Opinion in Genetics and Development 15, 542-547.
- Carpenter, B., Hill, K. J., Charalambous, M., Wagner, K. J., Lahiri, D., James, D. I., Anderson, J. S., Schumacher, V., Royer-Pokora, B., Mann,M., Ward, A. and Roberts, S.G.E. (2004). BASP1 is a transcriptional cosuppressor for the Wilms’ tumour suppressor protein WT1. Molecular and Cellular Biology 24, 537-549.
- Fairley, J.A., Evans, R., Hawkes, N.A. and Roberts, S.G.E. (2002). Core promoter-dependent TFIIB conformation and a role for TFIIB conformation in transcription start site selection. Molecular and Cellular Biology 22, 6697-6705.
- Richard, D.J., Schumacher, V., Royer-Pokora, B. and Roberts, S.G.E. (2001). Par 4 is a coactivator for a splice-isoform specific transcriptional activation domain in WT1. Genes and Development 15, 328-339.
- Evans, R., Fairley, J. A. and Roberts, S.G.E. (2001). Activator-mediated disruption of sequence-specific DNA contacts by the general transcription factor TFIIB. Genes and Development 15, 2945-2949.
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