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


CONCLUSIONS
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.
Huisinga
Kathryn L
KL
Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. khuising@artsci.wustl.edu
Pugh
B Franklin
BF
D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D008957:Models, Genetic; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein