Promoter
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DNA is fundamentally important for all cellular organisms due to its role as a store of hereditary genetic information. The precise and accurate regulation of gene transcription depends primarily on promoters, which vary significantly within and between genomes. Some promoters are rich in specific types of bases, while others have more varied, complex sequence characteristics. However, it is not only base sequence but also epigenetic modifications and altered DNA structure that regulate promoter activity. Significantly, many promoters across all organisms contain sequences that can form intrastrand hairpins (cruciforms) or four-stranded structures (G-quadruplex or i-motif). In this review we integrate recent studies on promoter regulation that highlight the importance of DNA structure in the evolutionary adaptation of promoter sequences.
Previous studies suggested that increased activity of haem oxygenase 1 may ameliorate autoimmune neuroinflammation in experimental models of multiple sclerosis. This increased activity is associated with an augmented number of GT repeats (≥ 25) within the HMOX1 gene promoter. Here we examined 338 patients with multiple sclerosis to determine the influence of their HMOX1 gene promoter (GT)n polymorphism and other individual characteristics on the course of the disease. The patients were divided into those with “rapid” or “delayed” course, based on reaching expanded disability status scale step 4 within nine years of disease onset, and the correlations between the disease course and the investigated characteristics were sought using logistic regression analysis. No statistically significant effect of HMOX1 gene promoter (GT)n polymorphism on the rate of disability progression was found (P = 0.9). This was confirmed by Cox regression analysis, which did not find any difference in the cumulative risk of reaching expanded disability status scale step 4 between the patients with long and short HMOX1 gene promoter (P = 0.7). In contrast, covariates significantly associated with the faster disability progression were: progressive course of multiple sclerosis, shorter duration of disease-modifying treatment and older age at disease onset (P ≤ 0.04). The observed absence of effect of the HMOX1 promoter (GT)n polymorphism could be attributed to its known dualistic role in the pathogenesis of autoimmune disorders. As a secondary outcome, we have seen that disease-modifying drugs have the potential to delay disability progression in patients with multiple sclerosis.
- MeSH
- autoimunitní nemoci genetika MeSH
- časové faktory MeSH
- dospělí MeSH
- genetické markery MeSH
- hemoxygenasa-1 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- prognóza MeSH
- progrese nemoci MeSH
- promotorové oblasti (genetika) MeSH
- proporcionální rizikové modely MeSH
- regresní analýza MeSH
- roztroušená skleróza genetika metabolismus MeSH
- věk při počátku nemoci MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Stalk lodging, which is generally determined by stalk strength, results in considerable yield loss and has become a primary threat to maize (Zea mays) yield under high-density planting. However, the molecular genetic basis of maize stalk strength remains unclear, and improvement methods remain inefficient. Here, we combined map-based cloning and association mapping and identified the gene stiff1 underlying a major quantitative trait locus for stalk strength in maize. A 27.2-kb transposable element insertion was present in the promoter of the stiff1 gene, which encodes an F-box domain protein. This transposable element insertion repressed the transcription of stiff1, leading to the increased cellulose and lignin contents in the cell wall and consequently greater stalk strength. Furthermore, a precisely edited allele of stiff1 generated through the CRISPR/Cas9 system resulted in plants with a stronger stalk than the unedited control. Nucleotide diversity analysis revealed that the promoter of stiff1 was under strong selection in the maize stiff-stalk group. Our cloning of stiff1 reveals a case in which a transposable element played an important role in maize improvement. The identification of stiff1 and our edited stiff1 allele pave the way for efficient improvement of maize stalk strength.
- MeSH
- alely MeSH
- buněčná stěna metabolismus MeSH
- CRISPR-Cas systémy MeSH
- fenotyp MeSH
- kukuřice setá genetika MeSH
- lignin metabolismus MeSH
- lokus kvantitativního znaku MeSH
- mapování chromozomů MeSH
- promotorové oblasti (genetika) * MeSH
- rostlinné geny MeSH
- rostlinné proteiny genetika metabolismus MeSH
- sekvenční analýza MeSH
- transformace genetická MeSH
- transpozibilní elementy DNA genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1β (IL-1β) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1β gene expression can be regulated by DNA methylation of its promoter. In the present study, we hypothesized that hypomethylation in the promoter region of the IL-1β gene may underlie its overexpression observed in TSC brain tissue. Bisulfite sequencing was used to study the methylation status of the promoter region of the IL-1β gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1β gene in TSC samples. IL-1β is overexpressed in tubers, and gene expression is correlated with promoter hypomethylation at CpG and non-CpG sites. Our results provide the first evidence of epigenetic modulation of the IL-1β signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1β-mediated inflammatory signaling in TSC brain.
- MeSH
- CpG ostrůvky MeSH
- dítě MeSH
- epigeneze genetická MeSH
- interleukin-1beta genetika metabolismus MeSH
- lidé MeSH
- metylace DNA * MeSH
- mladiství MeSH
- mozek metabolismus MeSH
- promotorové oblasti (genetika) * MeSH
- studie případů a kontrol MeSH
- tuberózní skleróza genetika metabolismus MeSH
- up regulace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Matrixmetaloproteinázy (MMP) představují skupinu volně cirkulujících enzymů i transmembránových proteinů se schopností rozrušovat extracelulární hmoty a bazální membrány za fyziologických i patologických podmínek. Tyto enzymy umožňují vznik prostředí vhodného k šíření nádorovému procesu. Zvýšená exprese matrixmetaloproteinázy -1 (MMPl) je spojena s počátečním růstem, s dalším šířením karcinomu a jeho metastazováním. Genový polymorfismus promotoru MMPl částečně reguluje genovou expresi tohoto enzymu. Alela 2G znamená zvýšenou transkripční aktivitu, která může být spojená se zvýšeným rizikem vzniku rakoviny plic. Cílem této analýzy bylo zkoumání vztahu mezi nukleotidovým polymorfismem MMPl a metastazováním plicní rakoviny. Celkem bylo vyšetřeno 154 pacientů, 95 s nemalobuněčnou plicní rakovinou a 59 s malobunečnou formou plicní rakoviny. Podle Časového vztahu ke vzniku metastáz byli všichni pacienti rozděleni do tří skupin. Skupina A představovala synchronní tsoučasně) diagnostikované vzdálené metastázy v době diagnózy plicní rakoviny. Skupina B zahrnovala asynchronní diagnostiku metastáz od 1 do 24 měsíců od doby diagnózy primárního nádoru. Skupina C představovala soubor nemocných bez vzdálených metastáz po dobu 2 let sledování od diagnostiky plicní rakoviny. Alelická četnost IG v metastazujících skupinách A+B byla zjištěna v 54 %; četnost 2G ve 46 %. V nemetastazující skupině C alelická četnost IG alely byla zjištěna v 51,7 % a 2G četnost ve 48,3 % případů. V práci nebylo zjištěno, že by se četnosti alel i genotipů mezi jednotlivými skupinami signifikantně lišila. Navíc je právě v nemetastazující skupině C proti očekávání vyšší zastoupení 2G alely. Polymorfismus 1G/2G v promotoru genu pro MMP-1 se tedy pravděpodobně nepodílí na progresi nádorového onemocnění.
Matrix metalloproteinases (MMP) are freely circulating or transmembraneous proteins capable of disrupting extracellular mass and basal membranes under both physiologicyal and pathological conditions. These enzymes promote an environment favourable to the spreading of tumorous processes. A stronger expression of MMP-1 is associated with the initial growth and subsequent spreading of lung carcinoma £ind its metastasizing. The gene polymorphysm of the MMP-1 promoter in part regulates the gene expression of this enzyme. Allele 2G stands for a higher transcription activity, which may go hand in hand with a higher risk of lung cancer. The purpose of our trial was to investigate the relation of MMP-1 nucleoid polymorphism and of metastasizing lung cancer. We examined 154 patients - 95 presented non-small-cell lung carcinoma, 59 its small-cell form. Patients were divided into three groups according to the onset of metastases. In Group A were distant metastases diagnosed simulaneously with the diagnosis of lung cancer. In Group B were metastases diagnosed 1 to 24 months after the diagnosis of the primary tumour. The patients in Group C were free of distant metastases throughout a two-year follow-up Since the diagnosis of lung carcinoma. The overall frequency of allele IG in the metastasizing groups A and B was 54 %, the frequency of 2G was 46 %. In the metastasis-free group C the frequency of allele IG was 51.7 %, of allele 2G 48.3 %. The trial revealed no significant differences in the frequency of alleles and of genotypes between individual groups. Rather unexpectedly in the metastasis-free group C there was a higher proportion of 2G allelic. Most probably the polymorphism 1G/2G in the promoter gene for MMP-1 is not involved in the progres sion of tumours.
- MeSH
- alely MeSH
- bronchogenní karcinom diagnóza patologie sekundární MeSH
- finanční podpora výzkumu jako téma MeSH
- genotyp MeSH
- lidé MeSH
- matrixové metaloproteinasy diagnostické užití genetika krev MeSH
- nádorové supresorové proteiny fyziologie MeSH
- nádory plic diagnóza sekundární MeSH
- onkogeny fyziologie MeSH
- polymorfismus genetický MeSH
- receptory růstových faktorů fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
Nucleoside-containing metabolites such as NAD+ can be incorporated as 5' caps on RNA by serving as non-canonical initiating nucleotides (NCINs) for transcription initiation by RNA polymerase (RNAP). Here, we report CapZyme-seq, a high-throughput-sequencing method that employs NCIN-decapping enzymes NudC and Rai1 to detect and quantify NCIN-capped RNA. By combining CapZyme-seq with multiplexed transcriptomics, we determine efficiencies of NAD+ capping by Escherichia coli RNAP for ∼16,000 promoter sequences. The results define preferred transcription start site (TSS) positions for NAD+ capping and define a consensus promoter sequence for NAD+ capping: HRRASWW (TSS underlined). By applying CapZyme-seq to E. coli total cellular RNA, we establish that sequence determinants for NCIN capping in vivo match the NAD+-capping consensus defined in vitro, and we identify and quantify NCIN-capped small RNAs (sRNAs). Our findings define the promoter-sequence determinants for NCIN capping with NAD+ and provide a general method for analysis of NCIN capping in vitro and in vivo.
- MeSH
- DNA řízené RNA-polymerasy metabolismus MeSH
- endoribonukleasy metabolismus MeSH
- Escherichia coli genetika metabolismus MeSH
- exprese genu genetika MeSH
- genetická transkripce genetika MeSH
- NAD metabolismus MeSH
- nukleotidy genetika MeSH
- počátek transkripce fyziologie MeSH
- promotorové oblasti (genetika) genetika MeSH
- RNA čepičky genetika MeSH
- transkriptom genetika MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, p = 0.003) and also total antioxidant capacity (p < 0.05), which showed a close positive relationship with serum bilirubin levels (p = 0.067) and the use of enzyme replacement therapy (p = 0.036). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27-0.97, p = 0.038). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.
- MeSH
- antioxidancia metabolismus MeSH
- bilirubin krev MeSH
- dospělí MeSH
- Fabryho nemoc krev enzymologie genetika MeSH
- glukuronosyltransferasa genetika MeSH
- hemoxygenasa-1 genetika MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- promotorové oblasti (genetika) MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Ovarian cancer is the leading cause of death from gynaecologic tumours, but the molecular and especially epigenetic events underlying the transformation are poorly understood. Various methylation changes have been identified and show promise as potential cancer biomarkers. The aim of this study was to investigate promoter methylation of selected tumour suppressor genes in ovarian cancer by comparison with normal ovarian tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification to compare the methylation status of 44 tissue samples of ovarian cancer with 30 control samples. Using a 20% cut-off for methylation, we observed significantly higher methylation in genes NTKR1, GATA4 and WIF1 in the ovarian cancer group compared with the control group. These findings could potentially be used in screening of ovarian cancer, and may have implications for future chemotherapy based on epigenetic changes.
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA genetika MeSH
- mladý dospělý MeSH
- nádorové supresorové proteiny genetika metabolismus MeSH
- nádory vaječníků genetika patologie MeSH
- promotorové oblasti (genetika) * MeSH
- receptor trkA genetika metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- transkripční faktor GATA4 genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
