The Basal Transcriptional Machinery
The identification and characterization of TSS regions, also called core promoter regions, is a pre-requisite for the understanding how Pol II transcription is controlled. Pol II is the core of the basal transcriptional machinery, which contains a large number of general transcription factors, many of them are summarized as the TFIID complex. Via another multi-protein complex of co-activators, termed Mediator, the basal transcriptional machinery is connected with activating and repressing cell- and site-specific transcription factors binding to genomic regions that are distal to the TSS region.
Whole genome sequencing and associated new technologies indicated that i) most human promoter regions do not contain a TATA box, ii) the TSS of many genes is not a single defined nucleotide and iii) most genes have multiple promoter regions. Alternative TSS usage generates diversity and complexity in the human transcriptome and the resulting proteome. A comprehensive survey of promoter regions is a major step towards understanding transcriptional control networks.
In this chapter, we will discuss how the basal transcriptional machinery assembles on the core promoter. We will understand the TATA box as the prototype of a site-specific transcription factor-binding site. The association of TBP with this site will introduce the principles of specific recognition of DNA and protein complex formation on it. We will learn that a number of alternative binding sites for general transcription factors allow the assembly of more or less the same multi-protein complex on the core promoter. Finally, we will recognize the Mediator as an evolutionarily conserved, multi-protein complex that interacts with a large variation of transcription factors and in parallel coordinates the action of co-activators and co-repressors, some of which are chromatin modifiers.