Transcription Factors

Every gene has a region known as the promoter. This is a DNA sequence "upstream" from the coding region, to which RNA polymerase must bind before it begins transcribing the coding region of the gene. In eukaryotes, the promoters of many (but not all) genes contain the sequence TATAA twenty-five to thirty nucleotides upstream from the transcription start site (T is the nucleotide adenine; A is thymine). Called the "TATA box," this sequence binds the TATA-binding protein (TBP), one of the most ancient and most important transcription factors.

The DNA-binding region of TBP has changed very little in millions of years of evolution, indicating how central this portion of the protein is in gene transcription. Transcription factors in archaeans are closely akin to those in eukaryotes, though simpler, and they reveal a deep evolutionary relation between the two groups. (Transcription factors are also used by eubacteria, but the details differ significantly and will not be discussed here.)

When TBP contacts DNA, the DNA bends. This distortion in shape allows the two sides of the double helix to come apart more easily. TATA-box DNA is especially easy to separate, because successive adenine-thymine pairs are somewhat less stable than series of other nucleotide pairs. The separation of the two strands makes the coding region of the gene more accessible to the RNA polymerase. (There are in fact three eukaryotic RNA polymerases, known as pol I, pol II, and pol III. Each uses a different set of transcription factors; we will discuss those for pol II.)

TBP plays a central role in initiating transcription, but it does not act alone. In archaeans, it works with another protein, transcription factor B. In eukaryotes, TBP is part of a larger complex, TFII-D (this rather colorless name is derived from "transcription factor D for RNA polymerase II"). TFII-D includes several other proteins besides TBP that interact with other factors and help stabilize the assembly on the DNA.

By itself, TFII-D cannot efficiently promote DNA-binding and transcription. Four other factors, TFII-B,-F,-E, and-H (binding in the order listed), allow pol II to bind to the promoter. Together, these are known as the basal transcription factors. Because each of these is composed of numerous individual polypeptides, the entire complex is thought to comprise at least twenty-five interacting polypeptides whose multiple interactions are critical for successful transcription.

The basal transcription factors assembled at the promoter are effective because they bind pol II. To finish their job, though, they must release Schematic diagram of a gene and its regulatory regions. TFII-D,-B,-F,-E, and-H are basal transcription factors, required for binding of RNA polymerase (pol II) to the promoter. Activators and repressors enhance or reduce the rate of gene transcription. it to begin transcription. This occurs when TFII-E and-H cooperate to phosphorylate (add a phosphate group to) RNA polymerase. This changes the polymerase's shape sufficiently to allow it to escape the complex of transcription factors and begin transcription.