10.7:
The Eukaryotic Promoter Region
The promoter is a major regulator of gene expression that contains binding sites for RNA polymerase, the enzyme responsible for transcription, and transcription factors, that facilitate or inhibit the binding of RNA polymerase.
The promoter region is mostly located upstream of the gene it regulates. It has distinct structural features, such as a curved structure with the ability to bend when transcriptional regulators bind and low thermodynamic stability due to the presence of AT-rich regions.
In eukaryotes, this transcriptional control region is more complex than in prokaryotes. In addition to the core promoter, eukaryotic genes have many additional cis-regulatory sequences that transcription factors can bind.
Prokaryotic RNA polymerase requires a sigma factor to bind to the promoter, whereas eukaryotic RNA polymerases require several such regulators.
Additionally, the three different RNA polymerases in eukaryotes that bind to distinct promoters, require different transcriptional regulators.
The core eukaryotic promoter contains several signature motifs that work together in various combinations to allow RNA polymerase to bind.
The TATA box is highly conserved across organisms. TATA boxes are usually present in genes that show high levels of cell-specific expression, such as proteins involved in cell differentiation.
Initiator and downstream promoter elements consist of degenerate sequences that follow a specific pattern of nucleotides, though their exact sequence varies.
The initiator element is the most common promoter motif. It can either help to maintain basal levels of transcription or work together with the TATA box to improve the binding of transcription factors.
The downstream promoter element is located downstream of the transcription start site and was initially found in promoters lacking a TATA box. The DPE often works in conjunction with the initiator element to regulate transcription.
CpG islands consist of sections of DNA where a cytosine is followed by a guanine. CpG islands usually regulate housekeeping genes, which are continuously expressed in small amounts and do not require high levels of transcription.
10.7:
The Eukaryotic Promoter Region
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are cis-regulatory sequences, thousands of base pairs away from a gene. The length of a promoter region can vary significantly from gene to gene.
The core promoter contains characteristic motifs where general transcription factors can bind and recruit RNA polymerase. The TATA box is a motif located 25-30 base pairs upstream from the transcription start site. It is more flexible and less thermodynamically stable than other promoter motifs due to its high A-T content, allowing the efficient binding of the transcription machinery. It is found in genes that require high levels of expression under specific conditions, such as those genes involved in cell differentiation. The TATA box is often flanked by a set of short nucleotide motifs, known as B-recognition elements. Transcription Factor II B, an important component involved in the assembly of the transcription machinery at the TATA box, binds to these B-elements.
The initiator element, composed of the degenerate sequence YYANWYY*, contains the transcription start site. Downstream of the initiator element is another characteristic motif, known as the downstream promoter element (DPE), made up of the degenerate sequence RGWYVT. The TATA box and the DPE regulate similar types of genes, and a eukaryotic promoter can have either a TATA box or a DPE. The initiator element can function synergistically either with a TATA box or DPE to regulate transcription.
The CpG islands are another type of core promoter motif that regulates the expression of other types of genes, like housekeeping genes, that require constant expression in small amounts. They are called CpG islands because they contain sequences that are high in cytosine followed by guanine. The “p” represents the phosphodiester bond that links C to G. CpG islands are also known to occur in distal promoter regions.
*R codes for either A or G; W codes for either A or T; Y codes for C or T; V codes for A or G or C; and N codes for any of the four bases.
Suggested Reading
- Alberts, Bruce, et al. Molecular Biology of the Cell. 6th ed. Garland Science, 2017. pp: 384-385
- Lodish, Harvey, et al. Molecular Cell Biology. 8th ed. W.H. Freeman and Company, 2016. pp: 371-372.
- Kiran, K., Ansari, S. A., Srivastava, R., Lodhi, N., Chaturvedi, C. P., Sawant, S. V., & Tuli, R. (2006). The TATA-box sequence in the basal promoter contributes to determining light-dependent gene expression in plants. Plant physiology, 142(1), 364–376. https://doi.org/10.1104/pp.106.084319
- Kanhere, A., & Bansal, M. (2005). Structural properties of promoters: similarities and differences between prokaryotes and eukaryotes. Nucleic acids research, 33(10), 3165–3175. https://doi.org/10.1093/nar/gki627
- Kutach, A. K., & Kadonaga, J. T. (2000). The downstream promoter element DPE appears to be as widely used as the TATA box in Drosophila core promoters. Molecular and cellular biology, 20(13), 4754–4764. https://doi.org/10.1128/mcb.20.13.4754-4764.2000
- Yella, V. R., & Bansal, M. (2017). DNA structural features of eukaryotic TATA-containing and TATA-less promoters. FEBS open bio, 7(3), 324–334. https://doi.org/10.1002/2211-5463.12166