Differential transcription regulation of eukaryotic protein-coding genes is controlled at multiple levels and involves the combinatorial function of regulatory DNA sequences and core promoter DNA elements. The core promoter is the minimal DNA region encompassing the transcription start site of a gene that is recognized by the ubiquitous basal/general transcription machinery and is sufficient to direct specific transcription initiation by RNA polymerase II in vitro. In contrast, regulatory DNA sequences are located at varying distances from the core promoter and are recognized by a variety of sequence-specific DNA-binding transcription regulators, which can be tissue-specific or developmentally regulated and influence the recruitment or activity of the basal transcription machinery at the core promoter. Thus, the core promoter and the associated basal transcription machinery are the ultimate targets of transcription regulatory signals. Significantly, the structure of the core promoter influences not only the basal activity of a promoter but also its selective response to specific enhancers and transcription regulators. How core promoters contribute to gene-selective transcription regulation is however unclear. Various core promoter DNA elements including the TATA box, the initiator, the DPE, and others have been identified. With the exception of the TATA box, the functions of the other elements are still poorly characterized. Surprisingly, recent analyses in Drosophila and humans have revealed that most protein-coding genes lack a TATA box. Although much has been learned about the mechanisms of transcription initiation and regulation of TATA box-containing genes, the basal machinery and the mechanisms of transcription initiation at the larger class of TATA-less genes remain poorly understood. Previous work by Dr. Martinez has indicated the existence of core promoter-specific basal factors and alternative pathways for specific transcription initiation at TATA-less core promoters. The specific research goals of this CAREER project are (i) to purify and identify the core promoter-specific basal factors that are essential for initiator function and initiator-dependent transcription from TATA-less promoters and (ii) to characterize the molecular functions of these core promoter-specific basal factors in vitro and in human cells. Through the educational component of this project (undergraduate and graduate courses in molecular biology, transcription and chromatin, and the development of a new undergraduate laboratory course focused on research in gene regulation, chromatin, and cell signaling), undergraduate, graduate and postdoctoral education and training in biochemistry and molecular biology will be enhanced. Participation of minority students at the University of California-Riverside will be emphasized. Undergraduate minority students in Dr. Martinez's laboratory have been participating in various "minority access programs" including the California Alliance for Minority Participation in Science (CAMP) program.
