On the Role of TATA Boxes and TATA-Binding Protein in Arabidopsis thaliana.

For transcription initiation by RNA polymerase II (Pol II), all eukaryotes require assembly of basal transcription machinery on the core promoter, a region located approximately in the locus spanning a transcription start site (-50; +50 bp). Although Pol II is a complex multi-subunit enzyme conserved among all eukaryotes, it cannot initiate transcription without the participation of many other proteins. Transcription initiation on TATA-containing promoters requires the assembly of the preinitiation complex; this process is triggered by an interaction of TATA-binding protein (TBP, a component of the general transcription factor TFIID (transcription factor II D)) with a TATA box. The interaction of TBP with various TATA boxes in plants, in particular Arabidopsis thaliana, has hardly been investigated, except for a few early studies that addressed the role of a TATA box and substitutions in it in plant transcription systems. This is despite the fact that the interaction of TBP with TATA boxes and their variants can be used to regulate transcription. In this review, we examine the roles of some general transcription factors in the assembly of the basal transcription complex, as well as functions of TATA boxes of the model plant A. thaliana. We review examples showing not only the involvement of TATA boxes in the initiation of transcription machinery assembly but also their indirect participation in plant adaptation to environmental conditions in responses to light and other phenomena. Examples of an influence of the expression levels of A. thaliana TBP1 and TBP2 on morphological traits of the plants are also examined. We summarize available functional data on these two early players that trigger the assembly of transcription machinery. This information will deepen the understanding of the mechanisms underlying transcription by Pol II in plants and will help to utilize the functions of the interaction of TBP with TATA boxes in practice.

An experimental study of the effects of SNPs in the TATA boxes of the GRIN1, ASCL3 and NOS1 genes on interactions with the TATA-binding protein.

The GRIN1, ASCL3, and NOS1 genes are associated with various phenotypes of neuropsychiatric disorders. For instance, these genes contribute to the development of schizophrenia, Alzheimer's and Parkinson's diseases, and epilepsy. These genes are also associated with various cancers. For example, ASCL3 is overexpressed in breast cancer, and NOS1, in ovarian cancer cell lines. Based on our findings and literature data, we had previously obtained results suggesting that the single-nucleotide polymorphisms (SNPs) that disrupt erythropoiesis are highly likely to be associated with cognitive and neuropsychiatric disorders in humans. In the present work, using SNP_TATA_Z-tester, we investigated the influence of unannotated SNPs in the TATA boxes of the promoters of the GRIN1, ASCL3, and NOS1 genes (which are involved in neuropsychiatric disorders and cancers) on the interaction of the TATA boxes with the TATA-binding protein (TBP). Double-stranded oligodeoxyribonucleotides identical to the TATA-containing promoter regions of the GRIN1, ASCL3, and NOS1 genes (reference and minor alleles) and recombinant human TBP were employed to study in vitro (by an electrophoretic mobility shift assay) kinetic characteristics of the formation of TBP-TATA complexes and their affinity. It was found, for example, that allele A of rs1402667001 in the GRIN1 promoter increases TBP-TATA affinity 1.4-fold, whereas allele C in the TATA box of the ASCL3 promoter decreases the affinity 1.4-fold. The lifetime of the complexes in both cases decreased by ~20 % due to changes in the rates of association and dissociation of the complexes (ka and kd, respectively). Our experimental results are consistent with the literature showing GRIN1 underexpression in schizophrenic disorders as well as an increased risk of cervical, bladder, and kidney cancers and lymphoma during ASCL3 underexpression. The effect of allele A of the -27G>A SNP (rs1195040887) in the NOS1 promoter is suggestive of an increased risk of ischemic damage to the brain in carriers. A comparison of experimental TBP-TATA affinity values (KD) of wild-type and minor alleles with predicted ones showed that the data correlate well (linear correlation coefficient r = 0.94, p <0.01).

A bioinformatic search for correspondence between differentially expressed genes of domestic versus wild animals and orthologous human genes altering reproductive potential.

One of the greatest achievements of genetics in the 20th century is D.K. Belyaev's discovery of destabilizing selection during the domestication of animals and that this selection affects only gene expression regulation (not gene structure) and inf luences systems of neuroendocrine control of ontogenesis in a stressful environment. Among the experimental data generalized by Belyaev's discovery, there are also f indings about accelerated extinc tion of testes' hormonal function and disrupted seasonality of reproduction of domesticated foxes in comparison with their wild congeners. To date, Belyaev's discovery has already been repeatedly conf irmed, for example, by independent observations during deer domestication, during the use of rats as laboratory animals, after the reintroduction of endangered species such as Przewalski's horse, and during the creation of a Siberian reserve population of the Siberian grouse when it had reached an endangered status in natural habitats. A genome-wide comparison among humans, several domestic animals, and some of their wild congeners has given rise to the concept of self-domestication syndrome, which includes autism spectrum disorders. In our previous study, we created a bioinformatic model of human self-domestication syndrome using differentially expressed genes (DEGs; of domestic animals versus their wild congeners) orthologous to the human genes (mainly, nervous-system genes) whose changes in expression affect reproductive potential, i. e., growth of the number of humans in the absence of restrictions caused by limiting factors. Here, we applied this model to 68 human genes whose changes in expression alter the reproductive health of women and men and to 3080 DEGs of domestic versus wild animals. As a result, in domestic animals, we identif ied 16 and 4 DEGs, the expression changes of which are codirected with changes in the expression of the human orthologous genes decreasing and increasing human reproductive potential, respectively. The wild animals had 9 and 11 such DEGs, respectively. This difference between domestic and wild animals was signif icant according to Pearson's χ2 test (p < 0.05) and Fisher's exact test (p < 0.05). We discuss the results from the standpoint of restoration of endangered animal species whose natural habitats are subject to an anthropogenic impact.

Promoters of genes encoding ß-amylase, albumin and globulin in food plants have weaker affinity for TATA-binding protein as compared to non-food plants: in silico analysis.

It is generally accepted that during the domestication of food plants, selection was focused on their productivity, the ease of their technological processing into food, and resistance to pathogens and environmental stressors. Besides, the palatability of plant foods and their health benefits could also be subjected to selection by humans in the past. Nonetheless, it is unclear whether in antiquity, aside from positive selection for beneficial properties of plants, humans simultaneously selected against such detrimental properties as allergenicity. This topic is becoming increasingly relevant as the allergization of the population grows, being a major challenge for modern medicine. That is why intensive research by breeders is already underway for creating hypoallergenic forms of food plants. Accordingly, in this paper, albumin, globulin, and ß-amylase of common wheat Triticum aestivum L. (1753) are analyzed, which have been identified earlier as targets for attacks by human class E immunoglobulins. At the genomic level, we wanted to find signs of past negative selection against the allergenicity of these three proteins (albumin, globulin, and ß-amylase) during the domestication of ancestral forms of modern food plants. We focused the search on the TATA-binding protein (TBP)-binding site because it is located within a narrow region (between positions -70 and -20 relative to the corresponding transcription start sites), is the most conserved, necessary for primary transcription initiation, and is the best-studied regulatory genomic signal in eukaryotes. Our previous studies presented our publicly available Web service Plant_SNP_TATA_Z-tester, which makes it possible to estimate the equilibrium dissociation constant (KD) of TBP complexes with plant proximal promoters (as output data) using 90 bp of their DNA sequences (as input data). In this work, by means of this bioinformatics tool, 363 gene promoter DNA sequences representing 43 plant species were analyzed. It was found that compared with non-food plants, food plants are characterized by significantly weaker affinity of TBP for proximal promoters of their genes homologous to the genes of common-wheat globulin, albumin, and ß-amylase (food allergens) (p < 0.01, Fisher's Z-test). This evidence suggests that in the past humans carried out selective breeding to reduce the expression of food plant genes encoding these allergenic proteins.

[Candidate SNP-markers altering TBP binding affinity for promoters of the Y-linked genes CDY2A, SHOX, and ZFY are lowering many indexes of reproductive potential in men]. / Кандидатные SNP-маркеры, изменяющие сродство ТВРк промоторам Y-ÑÐ²ÑÐ·Ð°Ð½Ð½Ñ‹Ñ Ð³ÐµÐ½Ð¾Ð² CDY2A, SHOX, ZFY, снижают ряд показателей репродуктивного потенциала мужчин.

Reproductive potential is the most important conditional indicator reflecting the ability of individuals in a population to reproduce, survive and develop under optimal environmental conditions. As for humans, the concept of reproductive potential can include the level of the individual's mental and physical state, which allows them to reproduce healthy offspring when they reach social and physical maturity. Female reproductive potential has been investigated in great detail, whereas the male reproductive potential (MRP) has not received the equal amount of attention as yet. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of MRP. With our development named Web-service SNP_TATA_Z-tester, we examined in silico all 35 unannotated SNPs within 70-bp proximal promoters of the three Y-linked genes, CDY2A, SHOX and ZFY, which represent all types of human Y-chromosome genes, namely: unique, pseudo-autosomal, and human X-chromosome gene paralogs, respectively. As a result, we found 11 candidate SNP markers for MRP, which can significantly alter the TATA-binding protein (TBP) binding affinity for promoters of these genes. First of all, we selectively verified in vitro the values of the TBP-promoter affinity under this study, Pearson's linear correlation between predicted and measured values of which were r = 0.94 (significance p < 0.005). Next, as a discussion, using keyword search tools of the PubMed database, we found clinically proven physiological markers of human pathologies, which correspond to a change in the expression of the genes carrying the candidate SNP markers predicted here. These were markers for spermatogenesis disorders (ZFY: rs1388535808 and rs996955491), for male maturation arrest (CDY2A: rs200670724) as well as for disproportionate short stature at Madelung deformity (e. g., SHOX: rs1452787381) and even for embryogenesis disorders (e. g., SHOX: rs28378830). This indicates a wide range of MRI indicators, alterations in which should be expected in the case of SNPs in the promoters of the human Y-chromosome genes and which can go far beyond changes in male fertility.