TATA box
In molecular biology, the TATA box is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has a shorter consensus sequence.
The TATA box is considered a non-coding DNA sequence. It was termed the "TATA box" as it contains a consensus sequence characterized by repeating T and A base pairs. How the term "box" originated is unclear. In the 1980s, while investigating nucleotide sequences in mouse genome loci, the Hogness box sequence was found and "boxed in" at the -31 position. When consensus nucleotides and alternative ones were compared, homologous regions were "boxed" by the researchers. The boxing in of sequences sheds light on the origin of the term "box".
The TATA box was first identified in 1978 as a component of eukaryotic promoters. Transcription is initiated at the TATA box in TATA-containing genes. The TATA box is the binding site of the TATA-binding protein and other transcription factors in some eukaryotic genes. Gene transcription by RNA polymerase II depends on the regulation of the core promoter by long-range regulatory elements such as enhancers and silencers. Without proper regulation of transcription, eukaryotic organisms would not be able to properly respond to their environment.
Based on the sequence and mechanism of TATA box initiation, mutations such as insertions, deletions, and point mutations to this consensus sequence can result in phenotypic changes. These phenotypic changes can then turn into a disease phenotype. Some diseases associated with mutations in the TATA box include gastric cancer, spinocerebellar ataxia, Huntington's disease, blindness, β-thalassemia, immunosuppression, Gilbert's syndrome, and HIV-1. The TATA-binding protein could also be targeted by viruses as a means of viral transcription.
History
Discovery
The TATA box was the first eukaryotic core promoter motif to be identified in 1978 by American biochemist David Hogness while he and his graduate student, Michael Goldberg were on sabbatical at the University of Basel in Switzerland. They first discovered the TATA sequence while analyzing 5' DNA promoter sequences in Drosophila, mammalian, and viral genes. The TATA box was found in protein coding genes transcribed by RNA polymerase II.Evolutionary history
Most research on the TATA box has been conducted on yeast, human, and Drosophila genomes, however, similar elements have been found in archaea and ancient eukaryotes. In archaea species, the promoter contains an 8 bp AT-rich sequence located ~24 bp upstream of the transcription start site. This sequence was originally called Box A, which is now known to be the sequence that interacts with the homologue of the archaeal TATA-binding protein. Also, even though some studies have uncovered several similarities, there are others that have detected notable differences between archaeal and eukaryotic TBP. The archaea protein exhibits a greater symmetry in its primary sequence and in the distribution of electrostatic charge, which is important because the higher symmetry lowers the protein's ability to bind the TATA box in a polar manner.Even though the TATA box is present in many eukaryotic promoters, it is not contained in the majority of promoters. One study found less than 30% of 1031 potential promoter regions contain a putative TATA box motif in humans. In Drosophila, less than 40% of 205 core promoters contain a TATA box. When there is an absence of the TATA box and TBP is not present, the downstream promoter element in cooperation with the initiator element bind to the transcription factor II D, initiating transcription in TATA-less promoters. The DPE has been identified in three Drosophila TATA-less promoters and in the TATA-less human IRF-1 promoter.
Features
Location
Promoter sequences vary between bacteria and eukaryotes. In eukaryotes, the TATA box is located 25 base pairs upstream of the start site that Rpb4/Rbp7 use to initiate transcription. In metazoans, the TATA box is located 30 base pairs upstream of the transcription start site. While in yeast, S. cerevisiae, the TATA box has a variable position which can range from 40 to 100 bp upstream of the start site. The TATA box is also found in 40% of the core promoters of genes that code for the actin cytoskeleton and contractile apparatus in cells.The type of core promoter affects the level of transcription and expression of a gene. TATA-binding protein can be recruited in two ways, by SAGA, a cofactor for RNA polymerase II, or by TFIID. When promoters use the SAGA/TATA box complex to recruit RNA polymerase II, they are more highly regulated and display higher expression levels than promoters using the TFIID/TBP mode of recruitment.
Analogous sequences
In bacteria, promoter regions may contain a Pribnow box, which serves an analogous purpose to the eukaryotic TATA box. The Pribnow box has a 6 bp region centered around the -10 position and an 8-12 bp sequence around the -35 region that are both conserved.A CAAT box is a region of nucleotides with the following consensus sequence: 5' GGCCAATCT 3'. The CAAT box is located about 75-80 bases upstream of the transcription initiation site and about 150 bases upstream of the TATA box. It binds transcription factors and thereby stabilizes the nearby preinitiation complex for easier binding of RNA polymerases. CAAT boxes are rarely found in genes that express proteins ubiquitous in all cell types.
Structure
Sequence and prevalence
The TATA box is a component of the eukaryotic core promoter and generally contains the consensus sequence 5'-TATAA-3'. In yeast, for example, one study found that various Saccharomyces genomes had the consensus sequence 5'-TATAA-3', yet only about 20% of yeast genes even contained the TATA sequence. Similarly, in humans only 24% of genes have promoter regions containing the TATA box. Genes containing the TATA-box tend to be involved in stress-responses and certain types of metabolism and are more highly regulated when compared to TATA-less genes. Generally, TATA-containing genes are not involved in essential cellular functions such as cell growth, DNA replication, transcription, and translation because of their highly regulated nature.The TATA box is usually located 25-35 base pairs upstream of the transcription start site. Genes containing the TATA box usually require additional promoter elements, including an initiator site located just upstream of the transcription start site and a downstream core element. These additional promoter regions work in conjunction with the TATA box to regulate initiation of transcription in eukaryotes.
Function
Role in transcription initiation
The TATA-box is the site of preinitiation complex formation, which is the first step in transcription initiation in eukaryotes. Formation of the preinitiation complex begins when the multi-subunit transcription factor II D binds to the TATA box at its TATA-binding protein subunit. TBP binds to the minor groove of the TATA box via a region of antiparallel β sheets in the protein. Three types of molecular interactions contribute to TBP binding to the TATA box:- Four phenylalanine residues on TBP bind to DNA and form kinks in the DNA, forcing the DNA minor groove open.
- Four hydrogen bonds form between polar side chains on TBP amino acid form between TBP residues and DNA bases, including van der Waals forces.
The conformational changes induced by TBP binding to the TATA box allows for additional transcription factors and RNA polymerase II to bind to the promoter region. TFIID first binds to the TATA box, facilitated by TFIIA binding to the upstream part of the TFIID complex. TFIIB then binds to the TFIID-TFIIA-DNA complex through interactions both upstream and downstream of the TATA box. RNA polymerase II is then recruited to this multi-protein complex with the help of TFIIF. Additional transcription factors then bind, first TFIIE and then TFIIH. This completes the assembly of the preinitiation complex for eukaryotic transcription.
This cluster of RNA polymerase II and various transcription factors is known as the basal transcriptional complex. In this state, it only gives a low level of transcription. Other factors must stimulate the BTC to increase transcription levels. One such example of a BTC stimulating region of DNA is the CAAT box. Additional factors, including the Mediator complex, transcriptional regulatory proteins, and nucleosome-modifying enzymes also enhance transcription in vivo.