TATA box
The TATA box is the binding site of the TATA-binding protein (TBP) 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.
[6] The TATA box was the first eukaryotic core promoter motif to be identified in 1978 by American biochemist David Hogness[1] while he and his graduate student, Michael Goldberg were on sabbatical at the University of Basel in Switzerland.
[2] 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.
One study found less than 30% of 1031 potential promoter regions contain a putative TATA box motif in humans.
In eukaryotes, the TATA box is located 25 base pairs upstream of the start site that Rpb4/Rbp7 use to initiate transcription.
[5] 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.
TATA-binding protein (TBP) can be recruited in two ways, by SAGA, a cofactor for RNA polymerase II, or by TFIID.
[12][14] 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.
[3] These additional promoter regions work in conjunction with the TATA box to regulate initiation of transcription in eukaryotes.
Formation of the preinitiation complex begins when the multi-subunit transcription factor II D (TFIID) binds to the TATA box at its TATA-binding protein (TBP) subunit.
[3] TBP binds to the minor groove[15] of the TATA box via a region of antiparallel β sheets in the protein.
[26] Interaction of TATA boxes with a variety of activators or repressors can influence the transcription of genes in many ways[citation needed].
One of the first studies of TATA box mutations looked at a sequence of DNA from Agrobacterium tumefaciens for the octopine type cytokinin gene.
[29] Point mutations to the TATA box have similar varying phenotypic changes depending on the gene that is being affected.
[31] Some diseases that can be caused due to this insufficiency by specific gene transcription are: Thalassemia,[32] lung cancer,[33] chronic hemolytic anemia,[34] immunosuppression,[35] hemophilia B Leyden,[36] and thrombophlebitis and myocardial infarction.
[38] This can be used to directly predict the phenotypic traits resulting from a selected mutation based on how tightly TBP is binding to the TATA box.
Mutations in the TATA box region affects the binding of the TATA-binding protein (TBP) for transcription initiation, which may cause carriers to have a disease phenotype.
Longer TATA box sequences correlates with higher levels of PG2 serum indicating gastric cancer conditions.
Blindness can be caused by excessive cataract formation when the TATA box is targeted by microRNAs to increase the level of oxidative stress genes.
[41] MicroRNAs can target the 3'-untranslated region and bind to the TATA box to activate the transcription of oxidative stress related genes.
[42] SNPs destabilize the TBP/TATA complex which significantly decreases the rate at which TATA-binding proteins (TBP) will bind to the TATA box.
[44] Novel HIV-1-encoded microRNA have been found to enhance the production of the virus as well as activating HIV-1 latency by targeting the TATA box region.
[5] Pharmaceutical companies have been designing cancer therapy drugs to target DNA in traditional methods over the years, and have proven to be successful.
In recent years, a collective effort has been made to find cancer-specific molecular targets, such as protein-DNA complexes, which include the TATA binding motif.
