A TATA binding protein regulatory network that governs transcription complex assembly.

Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. khuising@artsci.wustl.edu

BACKGROUND: Eukaryotic genes are controlled by proteins that assemble stepwise into a transcription complex. How the individual biochemically defined assembly steps are coordinated and applied throughout a genome is largely unknown. Here, we model and experimentally test a portion of the assembly process involving the regulation of the TATA binding protein (TBP) throughout the yeast genome. RESULTS: Biochemical knowledge was used to formulate a series of coupled TBP regulatory reactions involving TFIID, SAGA, NC2, Mot1, and promoter DNA. The reactions were then linked to basic segments of the transcription cycle and modeled computationally. A single framework was employed, allowing the contribution of specific steps to vary from gene to gene. Promoter binding and transcriptional output were measured genome-wide using ChIP-chip and expression microarray assays. Mutagenesis was used to test the framework by shutting down specific parts of the network. CONCLUSION: The model accounts for the regulation of TBP at most transcriptionally active promoters and provides a conceptual tool for interpreting genome-wide data sets. The findings further demonstrate the interconnections of TBP regulation on a genome-wide scale.

PMID: 17407552 [PubMed - indexed for MEDLINE]

PMCID: PMC1896006