Gene regulation plays a central role in all cellular functions, and alterations in this process have been associated with a number of developmental defects and disease states in humans. Initiation of gene expression requires changes to the chromatin environment of genes and the formation of the pre-initiation complex (PIC) at the promoter. The PIC is formed by the ordered recruitment of multiple general transcription factors (GTFs). Advances over the last five years indicate that chromatin is not simply an inert barrier to transcription, but may also play an important function in the recruitment of specific transcription factors to sites within the genome. Further, the distinction between the functions of GTFs and the chromatin remodeling machinery has been blurred by the discovery that certain GTFs have intrinsic chromatin modifying activities, or can recruit them to promoters. The overall goal of this proposal is to understand how chromatin remodeling complexes and Principal Investigator C components are recruited to repressed promoters, and how coordination of the chromatin remodeling and transcription steps occurs. We are using the DNA damage-responsive ribonucleotide reductase 3 gene (RNR3) of budding yeast to explore the functions of the TFIID complex, which is composed of the TATA-binding protein and 14 associated factors called TAFs. Our efforts over the last funding period revealed that TFIID is required for the recruitment of the SWI/SNF nucleosome remodeling complex and the remodeling of nucleosomes at the promoter of RNR3. The objectives of this proposal are to identify the features of RNR3 that confer its dependence upon TAFIIS and the general transcription machinery for nucleosome remodeling.
The aims of this proposal will address the role of transcription and the core promoter, identify the components of the pre-initiation complex (PIC) required for SWI/SNF recruitment, and analyze the interactions between PIC components, SWI/SNF and chromatin in an in vitro system. Further, we will explore the contributions of the """"""""histone code"""""""" in the remodeling and recruitment of transcription factors to RNR3 using genetic strategies to alter core histone modification states and mutating histone tails. These studies will define mechanisms of transcription factor recruitment, chromatin remodeling and the functions of the TFIID complex that will be applicable to other eukaryotic model systems. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058672-09
Application #
7162167
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Tompkins, Laurie
Project Start
1999-01-01
Project End
2007-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
9
Fiscal Year
2007
Total Cost
$291,743
Indirect Cost
Name
Pennsylvania State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Miller, Jason E; Zhang, Liye; Jiang, Haoyang et al. (2018) Genome-Wide Mapping of Decay Factor-mRNA Interactions in Yeast Identifies Nutrient-Responsive Transcripts as Targets of the Deadenylase Ccr4. G3 (Bethesda) 8:315-330
Crickard, John B; Lee, Jaehyoun; Lee, Tae-Hee et al. (2017) The elongation factor Spt4/5 regulates RNA polymerase II transcription through the nucleosome. Nucleic Acids Res 45:6362-6374
Crickard, J Brooks; Fu, Jianhua; Reese, Joseph C (2016) Biochemical Analysis of Yeast Suppressor of Ty 4/5 (Spt4/5) Reveals the Importance of Nucleic Acid Interactions in the Prevention of RNA Polymerase II Arrest. J Biol Chem 291:9853-70
Dutta, Arnob; Babbarwal, Vinod; Fu, Jianhua et al. (2015) Ccr4-Not and TFIIS Function Cooperatively To Rescue Arrested RNA Polymerase II. Mol Cell Biol 35:1915-25
Zheng, Suting; Crickard, J Brooks; Srikanth, Abhinaya et al. (2014) A highly conserved region within H2B is important for FACT to act on nucleosomes. Mol Cell Biol 34:303-14
Collart, Martine A; Reese, Joseph C (2014) Gene expression as a circular process: cross-talk between transcription and mRNA degradation in eukaryotes; International University of Andalusia (UNIA) Baeza, Spain. RNA Biol 11:320-3
Babbarwal, Vinod; Fu, Jianhua; Reese, Joseph C (2014) The Rpb4/7 module of RNA polymerase II is required for carbon catabolite repressor protein 4-negative on TATA (Ccr4-not) complex to promote elongation. J Biol Chem 289:33125-30
Reese, Joseph C (2013) The control of elongation by the yeast Ccr4-not complex. Biochim Biophys Acta 1829:127-33
Bhargava, Purnima; Reese, Joseph C (2013) Transcription by Odd Pols. Biochim Biophys Acta 1829:249-50
Miller, Jason E; Reese, Joseph C (2012) Ccr4-Not complex: the control freak of eukaryotic cells. Crit Rev Biochem Mol Biol 47:315-33

Showing the most recent 10 out of 32 publications