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At least 199 records · Page 11Linked to original sources
PubMed1988

Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter.

Plasminogen activator inhibitor type 1 is an important component of the fibrinolytic system and its biosynthesis is subject to complex regulation. To study this regulation at the level of transcription, we have identified and sequenced the promoter of the human plasminogen activator inhibitor type 1 gene. Nuclease protection experiments were performed by using endothelial cell mRNA and the transcription initiation (cap) site was established. Sequence analysis of the 5' flanking region of the gene revealed a perfect "TATA box" at position -28 to position -23, the conserved distance from the cap site. Comparative functional studies with the firefly luciferase gene as a reporter gene showed that fragments derived from this 5' flanking region exhibited high promoter activity when transfected into bovine aortic endothelial cells and mouse Ltk- fibroblasts but were inactive when introduced into HeLa cells. These studies indicate that the fragments contain the plasminogen activator inhibitor type 1 promoter and that it is expressed in a tissue-specific manner. Although the fragments were also silent in rat FTO2B hepatoma cells, their promoter activity could be induced up to 40-fold with the synthetic glucocorticoid dexamethasone. Promoter deletion mapping experiments and studies involving the fusion of promoter fragments to a heterologous gene indicated that dexamethasone induction is mediated by a glucocorticoid responsive element with enhancer-like properties located within the region between nucleotides -305 and +75 of the plasminogen activator inhibitor type 1 gene.

Amino Acid Sequence↗
PubMed1979

uvrC gene function in excision repair in toluene-treated Escherichia coli.

We have examined the role of the uvrC gene in UV excision repair by studying incision, excision, repair synthesis, and DNA strand reformation in Escherichia coli mutants made permeable to nucleoside triphosphates by toluene treatment. After irradiation, incisions occur normally in uvrC cells in the presence of nicotinamide mononucleotide (NMN), a ligase-blocking agent, but cannot be detected otherwise. We conclude that repair incisions are followed by a ligation event in uvrC mutants, masking incision. However, a uvrC polA12 mutant accumulates incisions only slightly less efficiently than a polA12 strain without NMN. Excision of pyrimidine dimers is defective in uvrC mutants (polA(+) or polA12) irrespective of the presence or absence of NMN. DNA polymerase I-dependent, NMN-stimulated repair synthesis, which is demonstrable in wild-type cells, is absent in uvrC polA(+) cells, but the uvrC polA12 mutant exhibits a UV-specific, ATP-dependent repair synthesis like parental polA12 strains. A DNA polymerase I-mediated reformation of high-molecular-weight DNA takes place efficiently in uvrC polA(+) mutants after incision accumulation, and the uvrC polA12 mutant shows more reformation than the polA12 strain after incision. These results indicate that normal incision occurs in uvrC mutants, but there appears to be a defect in the excision of pyrimidine dimers, allowing resealing via ligation at the site of the incision. The lack of NMN-stimulated repair synthesis in uvrC polA(+) cells indicates that incision is not the only requirement for repair synthesis.

DNA Polymerase I↗
PubMed1996

The NOT, SPT3, and MOT1 genes functionally interact to regulate transcription at core promoters.

Previous studies demonstrated that mutations in the Saccharomyces cerevisiae NOT genes increase transcription from TATA-less promoters. In this report, I show that in contrast, mutations in the yeast MOT1 gene decrease transcription from TATA-less promoters. I also demonstrate specific genetic interactions between the Not complex, Mot1p, and another global regulator of transcription in S. cerevisiae, Spt3p. Five distinct genetic interactions have been established. First, a null allele of SPT3, or a mutation in SPT15 that disrupts the interaction between Spt3p and TATA-binding protein (TBP), allele specifically suppressed the not1-2 mutation. Second, in contrast to not mutations, mutations in MOT1 decreased HIS3 and HIS4 TATA-less transcription. Third, not mutations suppressed toxicity due to overexpression of TBP in mot1-1 mutants. Finally, overexpression of SPT3 caused a weak Not- mutant phenotype in mot1-1 mutants. Collectively, these results suggest a novel type of transcriptional regulation whereby the distribution of limiting TBP (TFIID) on weak and strong TBP-binding core promoters is regulated: Mot1p releases stably bound TBP to allow its redistribution to low-affinity sites, and the Not proteins negatively regulate the activity of factors such as Spt3p that favor distribution of TBP to these low-affinity sites.

Adenosine Triphosphatases↗
PubMed2025

Role of functional genes for seed vigor related traits through genome-wide association mapping in finger millet (Eleusine coracana L. Gaertn.).

Finger millet (Eleusine coracana (L.) Gaertn.) is a calcium-rich, nutritious and resilient crop that thrives even in harsh environmental conditions. In such ecologies, seed longevity and seedling vigor are crucial for sustainable crop production amid climate change. The current study explores the genetics of accelerated aging on seed longevity traits across 221 diverse accessions of finger millet through genome-wide association approach (GWAS). A significant variation was identified in germination percentage, germination rate indices, mean germination time, seedling vigor indices and dry weight upon aging treatment. GWAS model from 11,832 high-quality SNPs identified through Genotyping-by-Sequencing (GBS) approach produced 491 marker-trait associations (MTAs) for 27 traits, of which 54 were FDR-corrected. A pleiotropic SNP, FM_SNP_9478 identified on chromosome 7B was associated with the traits viz., germination after aging, germination index after aging and their relative measures. Functional annotation revealed DET1 and expansin-A2 influenced seed coat integrity, critical for germination and aging resilience. Probable protein phosphatase 2C3 and piezo-type ion channels contributed to mechanical sensing and stress adaptation in seeds. Beta-amylase and acetyl-CoA carboxylase 2 were identified for seed metabolism and stress response. These insights lay the framework for targeted breeding efforts to improve seed quality and resilience under diverse production conditions.

Eleusine↗
PubMed1992

Expression of chimeric genes by the light-regulated cabII-1 promoter in Chlamydomonas reinhardtii: a cabII-1/nit1 gene functions as a dominant selectable marker in a nit1- nit2- strain.

In Chlamydomonas reinhardtii, expression of the cabII-1 gene increases dramatically in response to light (cabII-1 encodes one of the light-harvesting chlorophyll a/b-binding proteins of photosystem II). We have used a region upstream of the cabII-1 gene in translational fusions to the bacterial uidA gene (encodes beta-glucuronidase) and transcriptional fusions to the Chlamydomonas nitrate reductase gene (nit1). Chlamydomonas transformants carrying intact copies of the chimeric uidA gene do not express beta-glucuronidase at the level of enzyme activity or mRNA accumulation. Methylation in the cabII-1 promoter region of the introduced gene is extensive in these strains, suggesting that newly introduced foreign genes may be recognized and silenced by a cellular mechanism that is correlated with increased methylation. Transformants that express the chimeric cabII-1/nit1 gene have been recovered. In contrast to the endogenous nit1 gene, the chimeric cabII-1/nit1 gene is expressed in ammonium-containing medium. Moreover, nit1 mRNA accumulation is dramatically stimulated by light, with a time course that is indistinguishable from that of the endogenous cabII-1 gene. The cabII-1/nit1 gene has been used to select transformants in a nit1- nit2- Chlamydomonas strain (CC400G) and should be useful for transformation of the large number of mutants in the Ebersold-Levine lineage, which carry the same mutations.

Amino Acid Sequence↗
PubMed1995

Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis.

We report the complete genomic organization of the human WNT-5A gene, which encodes a cysteine-rich growth factor involved in cell-cell signaling during growth and differentiation. The gene comprises five exons with the terminal exon coding for a large 3'-untranslated region of approximately 6.5 kilobase pairs and utilizes multiple polyadenylation signals to generate at least four discrete transcripts. We discovered a new leader exon interrupted by a 411-base pair intron that was retained in our original cDNA cloning. The promoter region was located in a GpC-rich island and harbored numerous cis-acting elements including several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT boxes typical of housekeeping and growth factor genes. In support of this, primer extension revealed extension two transcription start sites. Transient cell transfection assays showed functional promoter activity for the 3.9-kilobase pair 5'-flanking region. Interestingly, internal and 5' deletions revealed tha the distal promoter was not required for full transcriptional activity and that the first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell carcinoma-associated translocation. In situ hybridization analyses of early human embryos at 28-42 days of gestation revealed that WNT-5A transcripts were not restricted to the developing brain and limbs but were also observed in the mesenchyme bordering the pharyngeal clefts and pouches and in the developing gonads and kidneys. The relatively high expression in the celomic epithelium and in the precursors of follicles and seminiferous tubules suggest a novel role for WNT-5A in germ-cell differentiation. This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene.

Animals↗
PubMed1980

Studies on the E. coli groNB (nusB) gene which affects bacteriophage lambda N gene function.

Escherichia coli mutants, called groNB, which block the growth of bacteriophage lambda at the level of action of the gene N product, have been isolated as survivors at 42 degrees C of bacteria carrying a) the defective prophage lambda bio11 i lambda cI857 delta H1 or b) the pcR1 plasmid containing the EcoRI immunity fragment of phage lambda cI857. In addition, groNB bacterial mutants have been isolated at 37 degrees C, as large colony formers in the presence of lambda i lambda cI h434, lambda i lambda cI h lambda, and lambda i lambda cI h80 phage. The groNB locus is located at 9 minute of the E. coli genetic map with the order of the neighboring loci being proC tsx groNB purE. Most groNB mutations isolated at 42 degrees C were found to interfere in addition with bacterial growth at low temperatures, since (a) the GroNB phenotypes of lambda growth inhibition and bacterial cold sensitivity cannot be separated by P1 transduction, and (b) some cold resistant revertants simultaneously become Gro+ for lambda growth. Lambda transducing phages carrying the groNB+ bacterial gene have been isolated. GroNB mutant bacteria lysogenized by the transducing phage acquire the Gro+ phenotype and simultaneously the cold resistant phenotype, suggesting that the groNB mutations are recessive to the wild-type gene.

Bacteriophage lambda↗
PubMed1993

Characterization of the 130-bp repeat enhancer element of the rat ribosomal gene: functional interaction with transcription factor E1BF.

The 130-bp repetitive element (RE) of the rat rDNA (ribosomal RNA-encoding gene) intergenic spacer stimulated the synthesis of rRNA four- to sixfold, in comparison with that of the promoter alone, both in vivo and in vitro, when ligated to the rat rDNA promoter. The addition of increasing amounts of highly purified E1BF (enhancer-1 binding factor), which binds to the rat rDNA promoter and an upstream nonrepetitive enhancer element [Zhang and Jacob, Mol. Cell. Biol. 10 (1990) 5177-5186], to an in vitro transcription system resulted in enhancement of rDNA transcription from the recombinant plasmids containing the promoter or promoter-RE. However, E1BF-mediated stimulation of transcription under the influence of the RE continued at higher concentrations of E1BF than did the control transcription from the promoter alone. The binding affinity of E1BF for the RE was comparable to its affinity for the nonrepetitive far upstream enhancer element previously characterized in our laboratory. The sequences protected by E1BF in the RE differed from those protected by UBF (upstream control element-binding factor), a well characterized pol I transcription factor. These data suggest that E1BF belongs to a class of transcription factors which interact with the promoter and spacer cis-acting RE to modulate rDNA transcription.

Animals↗
PubMed1976

Some genetic consequences of changes in the level of recA gene function in Escherichia coli K-12.

Genetic recombination was studied in E. coli mutants that carry lesions in the recA gene but retain some capacity for generating recombinant progeny. We observed that recombination was detectable only at a very low level during the incubation of leaky RecA- merozygotes in broth. However, recombination appeared to occur at much higher frequencies when recombinant progeny were assayed by selection on minimal agar. Analysis of the recombinants obtained with Hfr donors revealed a deficiency of multiple exchanges per unit length of DNA in leaky RecA- strains. In many of these crosses recombinants that inherited donor alleles close to the transfer origin were much reduced in frequency, except when the recipient was also RecB-.

Alleles↗
PubMed1996

Characterization of the functional gene encoding mouse class III alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) and an unexpressed processed pseudogene with an intact open reading frame.

Multiple forms of vertebrate alcohol dehydrogenase (ADH) have been identified, but only one form, class III ADH, has been conserved in all organisms studied. Class III ADH functions in vitro as a glutathione-dependent formaldehyde dehydrogenase, which suggests that this was the original function that drove the evolution of ADH. Genetic analysis of class III ADH in yeast supports this view, but such studies are lacking in higher eukaryotes. The mouse ADH family has been previously analyzed and it contains three forms of ADH including the class III enzyme. We have initiated a molecular genetic analysis of the mouse class III ADH gene (Adh-2) by screening a genomic library with a full-length cDNA. Two overlapping clones contained the complete Adh-2 gene composed of nine exons in a 12-kb region, with the placement of introns matching that observed in other mammalian ADH genes. In this screening, we also isolated a clone (psi Adh-2) that lacks introns and which resembles a processed pseudogene. psi Adh-2 contained 25 point mutations relative to the previously analyzed Adh-2 cDNA, but still retained an intact open reading frame. Northern blot analysis using gene-specific probes provided evidence that psi Adh-2 does not produce a mRNA in either liver or kidney, whereas Adh-2 does. The functionality of the two genes was also compared by fusion of their 5'-flanking regions to a lacZ reporter gene. Reporter gene expression following transfection into mouse F9 embryonal carcinoma cells indicated that only Adh-2 possesses promoter activity.

Aldehyde Oxidoreductases↗
PubMed1996

The cbpA chaperone gene function compensates for dnaJ in lambda plasmid replication during amino acid starvation of Escherichia coli.

We found previously that lambda plasmid DNA replication in amino acid-starved Escherichia coli relA mutants (i.e., during the relaxed response), which is carried out by the inherited replication complex, is dependent on functions of DnaK and GrpE molecular chaperones but proceeds in a dnaj mutant at a nonpermissive temperature. Here we demonstrate that this replication is inhibited when functions of both dnaJ and cbpA are impaired. In complete media, the growth of the lambda pi A66 phage (capable of replicating in E. coli dnaJ, dnaK, and grpE missense mutants at 30 degrees C), as well as efficiency of transformation by the lambda pi A66 plasmid, is significantly decreased in a dnaJ259 cbpA::kan double mutant. These results strengthen the proposal of other authors (C. Ueguchi, M. Kakeda, H. Yamada, and T. Mizuno, Proc. Natl. Acad. Sci. USA 91:1054-1058, 1994; C. Ueguchi, T. Shiozawa, M. Kakeda, H. Yamada, and T. Mizuno, J. Bacteriol. 177:3894-3896, 1995; and T. Yamashino, M. Kakeda, C. Ueguchi, and T. Mizuno, Mol. Microbiol. 13:475-483, 1994) that the cbpA gene product is a functional analog of the DnaJ chaperone in E. coli.

Amino Acids↗
PubMed1996

Allele specificity of the Escherichia coli dnaA gene function in the replication of plasmids derived from phage lambda.

We demonstrate a variation in the effects of seven alleles of the Escherichia coli dnaA gene, which cause temperature sensitivity of initiation of chromosomal replication, on the replication of lambda phage-derived plasmids at 30 degrees C. These mutants showed no allele specificity of dnaA function in replication of either of two lambda pi plasmids studied. On the other hand, the inability of the lambda P+ plasmid to replicate in dnaA508, 46 and 204 cells, in dnaB (groP A15) or in cells that are temperature sensitive for the chaperone genes dnaK756, dnaJ259 and grpE280 at 30 degrees C was suppressible by a single pi mutatation. This suggests that it is a common property of the pi protein, probably its weaker interaction with DnaB helicase, that is responsible for the suppression. One can also conclude that the DnaA-regulated transcriptional activation of ori lambda acts at the step, in which all these gene products cooperate, i.e. during preprimosome loading and chaperone-mediated release of DnaB from P protein inhibition.

Bacterial Proteins↗
PubMed2026

Characterization of the gut phageome and functional genes carried by phages in laying hens with fatty liver hemorrhagic syndrome.

BACKGROUND: The gut microbiota is closely associated with the development of fatty liver hemorrhagic syndrome (FLHS); however, the function of its viral component, particularly bacteriophages, remains poorly understood. This study compared clinical parameters and the cecal phageome between 30-week-old (W30) and 50-week-old (W50) laying hens to characterize gut phages in the context of this metabolic disorder. RESULTS: Clinical analysis revealed that the W50 group exhibited typical FLHS, accompanied by elevated serum liver function and lipid markers (P&#x2009;<&#x2009;0.05). Functional prediction of the gut microbiota suggested a reduced lipid-metabolic capacity in W50 compared to the W30 group. A total of 20,274 phage genomes were identified from the two groups. These phages were primarily classified into 67 viral families, including Salasmaviridae, Herelleviridae, Suoliviridae, Peduoviridae, Crevaviridae, and Casjensviridae. The families Druskaviridae, Felixviridae, and Stanwilliamsviridae were uniquely detected in the W50 group. The phage community structure differed significantly between groups, with both phage diversity and richness markedly lower in W50 (P&#x2009;<&#x2009;0.05). LEfSe analysis revealed that phage taxa such as Stegnyidae, Herpelidae, and Chasovidae were significantly enriched in the W50 group, whereas Crewdviridae, Salasmaviridae, and Castroviridae were predominantly enriched in the W30 group. Functional annotation showed that these phages encode numerous metabolism-related genes and carry antimicrobial resistance genes (ARGs) as well as virulence factor genes. Notably, the diversity of ARGs carried by W50 phages was significantly higher (P&#x2009;<&#x2009;0.05), and ARG-rank analysis indicated a greater potential risk to human health. CONCLUSIONS: This study provides the first characterization of the gut phageome associated with FLHS in laying hens and confirms that gut phages constitute an important reservoir of ARGs. These findings offer a new perspective for understanding the pathogenesis of this disease and its associated public health risks. Video Abstract.

Animals↗
PubMed1986

Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen.

The core gene of the hepatitis B virus genome contains two conserved in-phase initiation codons separated by about 90 nucleotides. This region ("the precore region") encodes largely hydrophobic amino acids. We have expressed the coding sequence of the core gene with or without the precore region by using a simian virus 40-derived vector in heterologous mammalian cells. The results show that the precore region is not required for the expression either of core antigen (cAg) or of a related hepatitis B virus antigen, the e antigen (eAg). However, the precore region causes the cAg to become associated with cytoplasmic membranes, probably the endoplasmic reticulum. Further, the presence of the precore sequence results in the secretion of eAg. Our results suggest that the precore region plays a role in targeting core proteins to the membrane; this may be the direct cause of eAg secretion and also may aid in the interaction of the core and surface antigens in the formation of the viral particle.

Animals↗