Activation of eukaryotic transcription depends on a refined interplay of regulatory proteins with their target genes. Our long-term goal is to elucidate the mechanisms underlying regulation of metazoan gene expression as a prerequisite for the development of diagnostic and therapeutic assays that detect and attenuate human diseases. The specific hypothesis behind the proposed research is that the """"""""TBP-associated factors"""""""" (TAFs) in the general transcription factor TFIID play an important role in metazoan transcription. That hypothesis is based on the observations that 1) mutations in TAFs are recessive lethal, 2.) TAFs interact with activators, 3.) TAFs mediate binding of TFIID to promoters, 4.) TAFs mediate the postsynthetic modification of histones and GTFs, and 5.) TAFs play an important role in various biological processes. Based on these results the main experimental focus of this proposal is on the functional importance of TAFs for transcription activation in the context of a metazoan genome.
The specific aims are to: 1. To dissect the functional importance of TAF1 activities in regulation of transcription. TAF1 plays an important role in transcription activation by postsynthetic modification of histones and GTFs, interacting with TBP, mediating the recruitment of TFIID to promoters. We will correlate genome-wide transcription profiling with chromatin immunoprecipitation experiments to elucidate the functional importance of the various activities in TAF1 in metazoan transcription. 2. To dissect the functional importance of TAFs in activation of transcription in Drosophila. The correlation of the transcription status of Drosophila genes with the presence of TAFs, TAF-mediated protein modifications, activators, and the RNA polymerase II transcription machinery (GTM) at promoters will elucidate the functional importance of TAFs in transcription activation. 3. To dissect the role of TAFs in the execution of biological processes in vivo. We will correlate the transcription of specific genes with the presence of TAFs, TAF-mediated protein modifications, and the GTM at the promoters of the genes to elucidate the functional importance of TAFs for body pattern formation, cell cycle progression, and epigemetic activation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM072847-04S1
Application #
7900256
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Tompkins, Laurie
Project Start
2009-09-18
Project End
2010-07-31
Budget Start
2009-09-18
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$137,692
Indirect Cost
Name
University of California Riverside
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521