An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> 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, ASCL...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2022-06-01
|
| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/3356 |
| _version_ | 1797213962299768832 |
|---|---|
| author | E. B. Sharypova I. A. Drachkova I. V. Chadaeva M. P. Ponomarenko L. K. Savinkova |
| author_facet | E. B. Sharypova I. A. Drachkova I. V. Chadaeva M. P. Ponomarenko L. K. Savinkova |
| author_sort | E. B. Sharypova |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-03-07T16:05:18Z |
| format | Article |
| id | doaj.art-a23192b3b2404920b465c541ec6bf998 |
| institution | Directory Open Access Journal |
| issn | 2500-3259 |
| language | English |
| last_indexed | 2024-04-24T11:06:36Z |
| publishDate | 2022-06-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj.art-a23192b3b2404920b465c541ec6bf9982024-04-11T15:31:04ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592022-06-0126322723310.18699/VJGB-22-291254An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding proteinE. B. Sharypova0I. A. Drachkova1I. V. Chadaeva2M. P. Ponomarenko3L. K. Savinkova4Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesThe 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).https://vavilov.elpub.ru/jour/article/view/3356<i>grin1</i><i>ascl3</i><i>nos1</i>tata-binding proteinaffinitytbp/tata interaction |
| spellingShingle | E. B. Sharypova I. A. Drachkova I. V. Chadaeva M. P. Ponomarenko L. K. Savinkova An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein Вавиловский журнал генетики и селекции <i>grin1</i> <i>ascl3</i> <i>nos1</i> tata-binding protein affinity tbp/tata interaction |
| title | An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein |
| title_full | An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein |
| title_fullStr | An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein |
| title_full_unstemmed | An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein |
| title_short | An experimental study of the effects of SNPs in the TATA boxes of the <i>GRIN1, ASCL3</i> and <i>NOS1</i> genes on interactions with the TATA-binding protein |
| title_sort | experimental study of the effects of snps in the tata boxes of the i grin1 ascl3 i and i nos1 i genes on interactions with the tata binding protein |
| topic | <i>grin1</i> <i>ascl3</i> <i>nos1</i> tata-binding protein affinity tbp/tata interaction |
| url | https://vavilov.elpub.ru/jour/article/view/3356 |
| work_keys_str_mv | AT ebsharypova anexperimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT iadrachkova anexperimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT ivchadaeva anexperimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT mpponomarenko anexperimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT lksavinkova anexperimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT ebsharypova experimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT iadrachkova experimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT ivchadaeva experimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT mpponomarenko experimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein AT lksavinkova experimentalstudyoftheeffectsofsnpsinthetataboxesoftheigrin1ascl3iandinos1igenesoninteractionswiththetatabindingprotein |