BACKGROUND: Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis-generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9. METHODS: Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients. RESULTS: CASP3 A+B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903-rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p=0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p=0.003). CONCLUSIONS: Genetic variability in CASP9 and expression of its splicing variants present targets for further study.

• MeSH
• cílená molekulární terapie * MeSH
• genetická transkripce * MeSH
• genetická variace * genetika   MeSH
• kaspasa 9 genetika   metabolismus   MeSH
• kaspasy * genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu * enzymologie   genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH

The present study was conducted to determine the gene responsible for beta-glucosidase (BGL) production and to generate a full-length complementary DNA (cDNA) of one of the putative BGL genes, which showed a significant expression level when Schizophyllum commune KUC9397 was grown in optimized medium. The relative expression levels of seven genes encoding BGL of S. commune KUC9397 were determined with real-time quantitative reverse transcription PCR in cellulose-containing optimized medium (OM) compared to glucose-containing basal medium (BM). The most abundant transcript was bgl3a in OM. The transcript number of the bgl3a increased more than 57.60-fold when S. commune KUC9397 was grown on cellulose-containing OM compared to that on glucose-containing BM. The bgl3a was identified, and a deduced amino acid sequence of bgl3a shared homology (97%) with GH3 BGL of S. commune H4-8. This is the first report showing the transcription levels of genes encoding BGL and identification of full-length cDNA of glycoside hydrolase 3 (GH3) BGL from S. commune. Furthermore, this study is one of the steps for consolidated bioprocessing of lignocellulosic biomass to bioethanol.

• MeSH
• aktivace transkripce MeSH
• beta-glukosidasa biosyntéza   genetika   MeSH
• kultivační média chemie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• molekulární sekvence - údaje MeSH
• Schizophyllum enzymologie   genetika   růst a vývoj   MeSH
• sekvence aminokyselin MeSH
• sekvenční analýza DNA MeSH
• sekvenční homologie aminokyselin MeSH
• stanovení celkové genové exprese * MeSH
• up regulace MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• DNA sondy analýza   genetika   MeSH
• exprese genu genetika   MeSH
• genetické techniky přístrojové vybavení   využití   MeSH
• molekulární biologie metody   přístrojové vybavení   MeSH
• stanovení celkové genové exprese metody   využití   MeSH

• MeSH
• genetická transkripce MeSH
• nukleoproteiny MeSH
• Orthomyxoviridae analýza   MeSH
• virové proteiny MeSH

The molecular mechanisms behind the transition from simple steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) are not clearly understood. This hinders development of effective therapies for treatment and prevention of NASH. In this study expression profiling data from normal, steatosis, and NASH human livers were used to predict transcription factors that are misregulated as mechanistic features of NAFLD progression. Previously-published human NAFLD gene expression profiling data from normal, steatosis, and NASH livers were subjected to transcription factor binding site enrichment analysis. Selected transcription factors that bind enriched transcription factor binding sites were analyzed for changes in expression. Distinct transcription factor binding sites were enriched in genes significantly up- or down-regulated in NASH livers. Those enriched in up-regulated genes were bound by transcription factors such as FOXA, CEBP, and HNF1 family members, while those enriched in down-regulated genes were bound by nuclear receptors involved in xenobiotic sensing and lipid metabolism. Levels of mRNA and protein for selected transcription factors were significantly changed during disease progression. The study indicates that NAFLD progression involves changes in activity or expression of transcription factors that regulate genes involved in hepatic processes known to be altered in NASH. Transcription factors such as PPAR receptors, FoxA family members, and HNF4A might be targeted therapeutically to prevent NAFLD progression.

• MeSH
• down regulace MeSH
• lidé MeSH
• nealkoholová steatóza jater metabolismus   MeSH
• progrese nemoci MeSH
• regulace genové exprese fyziologie   MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory metabolismus   MeSH
• up regulace MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The regulation of gene transcription allows yeast cells to respond properly to changing environmental conditions. Several protein complexes take part in this process. They involve RNA polymerase complexes, chromatin remodeling complexes, mediators, general transcription factors and specific transcriptional regulators. Using Saccharomyces cerevisiae as reference, the genomes of six species (Ashbya gossypii, Kluyveromyces lactis, K. waltii, Candida albicans, C. glabrata and Schizosaccharomyces pombe) that are human pathogens or important for the food industry were analyzed for their complement of genes encoding the homologous transcriptional regulators. The number of orthologs identified in a given species correlated with its phylogenetic distance from S. cerevisiae. Many duplicated genes encoding transcriptional regulators in S. cerevisiae and C. glabrata were reduced to one copy in species diverged before the ancestral whole genome duplication. Some transcriptional regulators appear to be specific for S. cerevisiae and probably reflect the physiological differences among species. Phylogenetic analysis and conserved gene order relationships indicate that a similar set of gene families involved in the control of multidrug resistance and oxidative stress response already existed in the common ancestor of the compared fungal species.

• MeSH
• fungální léková rezistence MeSH
• fungální proteiny genetika   chemie   metabolismus   MeSH
• fylogeneze MeSH
• genetická transkripce MeSH
• genom fungální MeSH
• kvasinky MeSH
• molekulární sekvence - údaje MeSH
• regulace genové exprese u hub MeSH
• sekvence aminokyselin MeSH
• transkripční faktory genetika   chemie   metabolismus   MeSH

CREB2 and CREB3 are two important members of the ATF/CREB family, which negatively and positively regulates CRE-dependent transcription in vitro. Here we report the cloning, chromosome mapping and tissue transcription analysis of CREB2 and CREB3 in pigs. The full-length coding sequence of CREB2 and CREB3 is 1047 bp and 1098 bp, encoding 348 and 365 amino acids, respectively. Porcine CREB3 comprises nine exons and eight introns, whereas CREB2 consists of three exons and two introns. CREB2 and CREB3 were cytogenetically assigned to porcine chromosome 5p and 1q28, respectively. Tissue transcription analysis revealed that both porcine CREB2 and CREB3 mRNA were ubiquitously detected in all examined tissues. Additionally, we cloned the 5' flank genomic sequence of porcine CREB3 and characterized several putative transcription factor recognition sites including SP1, NF-kappaB, AP-1 and AP-2 in its promoter region. Our studies provide basic molecular information helpful for further investigation of the function of the two genes in pig models.

• MeSH
• financování organizované MeSH
• fylogeneze MeSH
• genetická transkripce genetika   MeSH
• genom genetika   MeSH
• klonování DNA MeSH
• mapování chromozomů MeSH
• molekulární sekvence - údaje MeSH
• otevřené čtecí rámce genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protein vázající cAMP responzivní element genetika   chemie   MeSH
• regulace genové exprese MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• stanovení celkové genové exprese MeSH
• Sus scrofa genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5' UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

• MeSH
• genetická transkripce genetika   MeSH
• hypertenze * genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• promotorové oblasti (genetika) genetika   MeSH
• sekvenční analýza RNA metody   MeSH
• stanovení celkové genové exprese metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A test-statistic typically employed in the gene set enrichment analysis (GSEA) prevents this method from being genuinely multivariate. In particular, this statistic is insensitive to changes in the correlation structure of the gene sets of interest. The present paper considers the utility of an alternative test-statistic in designing the confirmatory component of the GSEA. This statistic is based on a pertinent distance between joint distributions of expression levels of genes included in the set of interest. The null distribution of the proposed test-statistic, known as the multivariate N-statistic, is obtained by permuting group labels. Our simulation studies and analysis of biological data confirm the conjecture that the N-statistic is a much better choice for multivariate significance testing within the framework of the GSEA. We also discuss some other aspects of the GSEA paradigm and suggest new avenues for future research.

• MeSH
• fenotyp MeSH
• financování organizované MeSH
• modely genetické MeSH
• multivariační analýza MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů statistika a číselné údaje   MeSH
• stanovení celkové genové exprese statistika a číselné údaje   MeSH
• výpočetní biologie MeSH

Bordetella pertussis is the causative agent of whooping cough, a respiratory disease still considered as a major public health threat and for which recent re-emergence has been observed. Constant reshuffling of Bordetella pertussis genome organization was observed during evolution. These rearrangements are essentially mediated by Insertion Sequences (IS), a mobile genetic elements present in more than 230 copies in the genome, which are supposed to be one of the driving forces enabling the pathogen to escape from vaccine-induced immunity. Here we use high-throughput sequencing approaches (RNA-seq and differential RNA-seq), to decipher Bordetella pertussis transcriptome characteristics and to evaluate the impact of IS elements on transcriptome architecture. Transcriptional organization was determined by identification of transcription start sites and revealed also a large variety of non-coding RNAs including sRNAs, leaderless mRNAs or long 3' and 5'UTR including seven riboswitches. Unusual topological organizations, such as overlapping 5'- or 3'-extremities between oppositely orientated mRNA were also unveiled. The pivotal role of IS elements in the transcriptome architecture and their effect on the transcription of neighboring genes was examined. This effect is mediated by the introduction of IS harbored promoters or by emergence of hybrid promoters. This study revealed that in addition to their impact on genome rearrangements, most of the IS also impact on the expression of their flanking genes. Furthermore, the transcripts produced by IS are strain-specific due to the strain to strain variation in IS copy number and genomic context.

• MeSH
• 3' nepřekládaná oblast MeSH
• 5' nepřekládaná oblast MeSH
• bakteriální RNA genetika   MeSH
• Bordetella pertussis genetika   MeSH
• genetická transkripce * MeSH
• genom bakteriální genetika   MeSH
• messenger RNA genetika   MeSH
• nekódující RNA genetika   MeSH
• počátek transkripce MeSH
• stanovení celkové genové exprese * MeSH
• transpozibilní elementy DNA genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH