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Gene Promoter Regions (gene + promoter_regions)
Selected AbstractsProteomic analysis of liver cancer cells treated with 5-Aza-2,-deoxycytidine (AZA),DRUG DEVELOPMENT RESEARCH, Issue 1 2009Shujun Bai Abstract 5-Aza-2,-deoxycytidine (AZA) is a potent inhibitor of DNA methylation that exhibits anti-tumor activity in a variety of tumor cells via reactivation of tumor suppressor genes. However, few studies have been done on the biological and clinical significance of AZA in human hepatocellular carcinoma. To identify potential genes that may be aberrantly methylated and confer growth advantage to neoplastic cells and to better understand the molecular mechanism(s) underlying AZA anti-tumor activity, a proteomics approach was used to annotate global gene expression changes of HepG2 cell line pre- and post-treatment with AZA. A total of 56 differentially expressed proteins were identified by 2D gel analysis, 48 of which were up-regulated while the remaining 8 were down regulated. Among the identified proteins, eight of these showed marked changed proteins, including seven up-regulated proteins: glutathione S-transferase P, protein DJ-1, peroxiredoxin-2, UMP-CMP kinase, cytochrome c-type heme lyase, enhancer of rudimentary homolog, profilin-1, and one down-regulated protein, heat-shock protein ,,1. The possible implication of these proteins in hepatocarcinogenesis is discussed. We tested two up-regulated proteins, glutathione S-transferase P and peroxiredoxin-2, using RT-PCR and their expression was consistent with the results obtained in the protein level. Both of these genes were methylated when methylation-specific PCR was used against their promoter regions. Following treatment with AZA, the gene promoter regions were found to be unmethylated, concomitant with overexpression of the proteins compared to HepG2 cells without treatment. These data provide useful information in evaluating the therapeutic potential of AZA for the treatment of HCC. Drug Dev Res 69, 2009. © 2009 Wiley-Liss, Inc. [source] THE EVOLUTION OF THE VERTEBRATE ,-GLOBIN GENE PROMOTEREVOLUTION, Issue 2 2002Nadia A. Chuzhanova Abstract Complexity analysis is capable of highlighting those gross evolutionary changes in gene promoter regions (loosely termed "promoter shuffling") that are undetectable by conventional DNA sequence alignment. Complexity analysis was therefore used here to identify the modular components (blocks) of the orthologous ,-globin gene promoter sequences of 22 vertebrate species, from zebrafish to humans. Considerable variation between the ,-globin gene promoters was apparent in terms of block presence/absence, copy number, and relative location. Some sequence blocks appear to be ubiquitous, whereas others are restricted to a specific taxon. Block similarities were also evident between the promoters of the paralogous human ,-like globin genes. It may be inferred that a wide variety of different mutational mechanisms have operated upon the ,-globin gene promoter over evolutionary time. Because these include gross changes such as deletion, duplication, amplification, elongation, contraction, and fusion, as well as the steady accumulation of single base-pair substitutions, it is clear that some redefinition of the term "promoter shuffling" is required. This notwithstanding, and as previously described for the vertebrate growth hormone gene promoter, the modular structure of the ,-globin promoter region and those of its paralogous counterparts have continually been rearranged into new combinations through the alteration, or shuffling, of preexisting blocks. Some of these changes may have had no influence on promoter function, but others could have altered either the level of gene expression or the responsiveness of the promoter to external stimuli. The comparative study of vertebrate ,-globin gene promoter regions described here confirms the generality of the phenomenon of sequence block shuffling and thus supports the view that it could have played an important role in the evolution of differential gene expression. [source] Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokersINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Sabine Zöchbauer-Müller Abstract An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor ,-2 (RAR,- 2), CDH13 (H-cadherin), p16INK4a (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RAR,- 2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens. © 2003 Wiley-Liss, Inc. [source] Heat shock proteins (chaperones) in fish and shellfish and their potential role in relation to fish health: a reviewJOURNAL OF FISH DISEASES, Issue 10 2010R J Roberts Abstract Heat shock proteins (HSPs), also known as stress proteins and extrinsic chaperones, are a suite of highly conserved proteins of varying molecular weight (c. 16,100 kDa) produced in all cellular organisms when they are exposed to stress. They develop following up-regulation of specific genes, whose transcription is mediated by the interaction of heat shock factors with heat shock elements in gene promoter regions. HSPs function as helper molecules or chaperones for all protein and lipid metabolic activities of the cell, and it is now recognized that the up-regulation in response to stress is universal to all cells and not restricted to heat stress. Thus, other stressors such as anoxia, ischaemia, toxins, protein degradation, hypoxia, acidosis and microbial damage will also lead to their up-regulation. They play a fundamental role in the regulation of normal protein synthesis within the cell. HSP families, such as HSP90 and HSP70, are critical to the folding and assembly of other cellular proteins and are also involved in regulation of kinetic partitioning between folding, translocation and aggregation within the cell. HSPs also have a wider role in relation to the function of the immune system, apoptosis and various facets of the inflammatory process. In aquatic animals, they have been shown to play an important role in health, in relation to the host response to environmental pollutants, to food toxins and in particular in the development of inflammation and the specific and non-specific immune responses to bacterial and viral infections in both finfish and shrimp. With the recent development of non-traumatic methods for enhancing HSP levels in fish and shrimp populations via heat, via provision of exogenous HSPs or by oral or water administration of HSP stimulants, they have also, in addition to the health effects, been demonstrated to be valuable in contributing to reducing trauma and physical stress in relation to husbandry events such as transportation and vaccination. [source] Interaction between Fibrinogen and IL-6 Genetic Variants and Associations with Cardiovascular Disease Risk in the Cardiovascular Health StudyANNALS OF HUMAN GENETICS, Issue 1 2010Cara L. Carty SUMMARY The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen concentrations, carotid intima-media thickness, and myocardial infarction or ischemic stroke in 3900 European-American Cardiovascular Health Study participants. To identify combinations of genetic main effects and interactions associated with outcomes, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were significantly associated with fibrinogen level (p < 0.005), but not with other outcomes. Fibrinogen levels were higher in individuals having FGB1437 (rs1800790) and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p= 0.03) interactions between IL-6 level and FGA and FGG promoter SNPs associated with fibrinogen levels were detected. We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD. [source] | |||||||||||||