Prediction and verification of the influence of the rs367781716 SNP on the interaction of the ТАТА-binding protein with the promoter of the human АВСА9 gene

Arkova, Olga; Драчкова, И. А.; Arshinova, T. V.; Рассказов, Д. А.; Суслов, В. В.; Пономаренко, П. М.; Пономаренко, М. П.; Kolchanov, Nikolay А.; Савинкова, Л. К.

doi:10.1134/s2079059716070029

Cited by 3 publications

(5 citation statements)

References 32 publications

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“…Within Tikhonov’s regularization [ 61 ], this correlation ( Figure 2 a) characterizes a similarity between the ill-posed inverse problem of evaluating the transcriptional outcome of mutations in plant proximal promoters ( Figure 1 ) and the analogous well-posed problem for humans, which has already been solved using our public Web service Human_SNP_TATA_Z-tester [ 28 ] (see in-depth description in the Supplementary Materials [ 18 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 62 , 63 , 64 , 65 , 66 , 67 ]). With this in mind, Figure 2 depicts how we adapted it step-by-step for comparing between wildtype and mutant variants of the plant promoter DNA sequences under study in their effects on gene expression, i.e., our new Web service Plant_SNP_TATA_Z-tester created in this work.…”

Section: Resultsmentioning

confidence: 99%

“…We processed DNA sequences by means of our public Web service Plant_SNP_TATA_Z-tester (e.g., Figure 3 a and Figure 6 ) created in this work, as depicted in Figure 2 . To this end, as its prototype, we used our previously developed Web service Human_SNP_TATA_Z-tester [ 28 ] (see description [ 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 62 , 63 , 64 , 65 , 66 , 67 ] in the Supplementary Materials ), and we expanded it only with Equation (2) in line with Tikhonov’s regularization [ 61 ].…”

Section: Methodsmentioning

confidence: 99%

“…( a ) The interchangeability of hsTBP ( x -axis) and atTBP ( y -axis) for transcription in vitro [ 45 ]. ( b ) Using Human_SNP_TATA_Z-tester [ 28 ] (see in-depth description in the Supplementary Materials [ 18 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 62 , 63 , 64 , 65 , 66 , 67 ]), we estimated the −ln(K D; hsTBP ) values of hsTBP affinity for the 90 bp DNA sequence of either the wildtype or the mutant variant of the Agrobacterium tumefaciens T-DNA TC7 promoter ( AtTC7 ) [ 54 ] from [ 45 ], as shown by arrow 1. ( c ) Statistically significant linear regression of the predicted K D;hsTBP values in relation to the F hsTBP values measured using hsTBP [ 45 ], as expressed by Equation (1) written above the dashed line.…”

Section: Figurementioning

confidence: 99%

“…It uses a step-by-step approximation [ 29 ]: (i) TBP slides along DNA [ 18 ]; (ii) TBP stops at the best TBP-binding site [ 30 , 31 ]; (iii) the TBP–promoter complex is fixed by the DNA bending at a right angle [ 32 ], as proven experimentally [ 33 ]. Subsequently, using Human_SNP_TATA_Z-tester, we analyzed 15243 SNPs, which yielded 3229 candidate SNP markers aggravating or relieving the development of human disorders, such as subfertility [ 28 , 34 ], obesity [ 35 ], hypertension [ 36 ], cognitive disorders [ 37 ], atherosclerosis [ 38 ], Alzheimer’s disease [ 39 , 40 ], hematopoietic disorders [ 41 ], and many others (for a review, see [ 42 ]). Lastly, from article to article, we selectively experimentally verified these predictions, as did some independent researchers (e.g., see [ 43 ]).…”

Section: Introductionmentioning

confidence: 99%

“…The supporting information can be downloaded at . References [ 18 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 62 , 63 , 64 , 65 , 66 , 67 ] are cited in the Supplementary Materials.…”

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Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression

Рассказов

Chadaeva

Sharypova

et al. 2022

IJMS

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Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data—on mutational effects in plant proximal promoters on gene expression—that we could find in PubMed. Some of these datasets cast doubt on both the existence and the uniqueness of the sought solution, which could unequivocally estimate effects of proximal promoter mutation on gene expression when plants are grown under various environmental conditions during their development. This means that the inverse problem under study is ill-posed. Furthermore, we found experimental data on in vitro interchangeability of plant and human TATA-binding proteins allowing the application of Tikhonov’s regularization, making this problem well-posed. Within these frameworks, we created our Web service Plant_SNP_TATA_Z-tester and then determined the limits of its applicability using those data that cast doubt on both the existence and the uniqueness of the sought solution. We confirmed that the effects (of proximal promoter mutations on gene expression) predicted by Plant_SNP_TATA_Z-tester correlate statistically significantly with all the experimental data under study. Lastly, we exemplified an application of Plant_SNP_TATA_Z-tester to agriculturally valuable mutations in plant promoters.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression

Рассказов

Chadaeva

Sharypova

et al. 2022

IJMS

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Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis

Otálora‐Otálora

Osuna-Garzón

Carvajal

et al. 2022

Biology

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The bioinformatic pipeline previously developed in our research laboratory is used to identify potential general and specific deregulated tumor genes and transcription factors related to the establishment and progression of tumoral diseases, now comparing lung cancer with other two types of cancer. Twenty microarray datasets were selected and analyzed separately to identify hub differentiated expressed genes and compared to identify all the deregulated genes and transcription factors in common between the three types of cancer and those unique to lung cancer. The winning DEGs analysis allowed to identify an important number of TFs deregulated in the majority of microarray datasets, which can become key biomarkers of general tumors and specific to lung cancer. A coexpression network was constructed for every dataset with all deregulated genes associated with lung cancer, according to DAVID’s tool enrichment analysis, and transcription factors capable of regulating them, according to oPOSSUM´s tool. Several genes and transcription factors are coexpressed in the networks, suggesting that they could be related to the establishment or progression of the tumoral pathology in any tissue and specifically in the lung. The comparison of the coexpression networks of lung cancer and other types of cancer allowed the identification of common connectivity patterns with deregulated genes and transcription factors correlated to important tumoral processes and signaling pathways that have not been studied yet to experimentally validate their role in lung cancer. The Kaplan–Meier estimator determined the association of thirteen deregulated top winning transcription factors with the survival of lung cancer patients. The coregulatory analysis identified two top winning transcription factors networks related to the regulatory control of gene expression in lung and breast cancer. Our transcriptomic analysis suggests that cancer has an important coregulatory network of transcription factors related to the acquisition of the hallmarks of cancer. Moreover, lung cancer has a group of genes and transcription factors unique to pulmonary tissue that are coexpressed during tumorigenesis and must be studied experimentally to fully understand their role in the pathogenesis within its very complex transcriptomic scenario. Therefore, the downstream bioinformatic analysis developed was able to identify a coregulatory metafirm of cancer in general and specific to lung cancer taking into account the great heterogeneity of the tumoral process at cellular and population levels.

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Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

Zolotareva,

Dotsenko,

Podkolodnyy

et al. 2024

IJMS

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Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes’ promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, and GeneMANIA—as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.

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Prediction and verification of the influence of the rs367781716 SNP on the interaction of the ТАТА-binding protein with the promoter of the human АВСА9 gene

Cited by 3 publications

References 32 publications

Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression

Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression

Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis

Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

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