Cell Biology and Metabolism Branch
NICHD
Building 18T, Room 101
Bethesda, MD 20892
Phone: (301) 402-8532
Fax: (301) 402-0078
E-mail: wass@helix.nih.gov
Laboratory location: Building 32T-II
We are using genetic and molecular approaches to investigate roles for transcriptional coactivators, TAFs (TBP associated factors) in regulating transcription during Drosophila development. In Drosophila eight TAFs ranging in size from 30-250 kD have been biochemically purified as components of the TFIID complex. In vitro studies of reconstituted TFIID complexes have begun to identify interactions that these TAFs make within the TFIID complex and with transcriptional activators that are required for activated transcription. It appears that transcriptional regulation of some genes may require different combinations of these TAFs or possibly additional substoichiometric TAFs.
We have isolated mutations in several TAF genes as dominant suppressors of a rough eye phenotype caused by eye-specific expression of a Ras1 transgene under regulatory control of the sevenless promoter and enhancer. TAF mutations act as suppressors in this system by reducing the level of transcription of the Ras1 transgene. Flies carrying mutations in TAFs were used to demonstrate that interactions between the transcriptional activator Bicoid and TAFs are required to activate zygotic Hunchback transcription during the process of embryonic pattern formation. Thus, this genetic system in Drosophila presents the opportunity to identify and study the function of components of the transcriptional machinery, like TAFs, that play critical roles in regulating transcription in developmentally complex organisms.
Wassarman, D. A., Solomon, N. M., Chang, H. C., Karim, F. D., Therrien, M., and Rubin, G. M. (1996). Protein phosphatase 2A positively and negatively regulates Ras1-mediated photoreceptor development in Drosophila. Genes Dev. 10, 272-278.
Karim, F. D., Chang, H. C., Therrien, M., Wassarman, D. A., Laverty, T., and Rubin, G. M. (1996). A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics 143, 315-327.
Therrien, M., Chang, H. C., Solomon, N. M., Karim, F. D., Wassarman, D. A., and Rubin, G. M. (1995). KSR, a novel protein kinase required for Ras signal transduction. Cell 83, 879-888.
Wassarman, D. A., Therrien, M., and Rubin, G. M. (1995). The Ras signaling pathway in Drosophila. Curr. Op. Genet. Dev. 5, 44-50.
Two post-doctoral positions are currently available to study the
role of Drosophila TAFs in transcriptional regulation in vivo. Please
direct inquiries to David Wassarman at the address listed above.