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At least 235 records · Page 13Linked to original sources
PubMed1974

Analysis of bacteriophage phi 29 gene function: protein synthesis in suppressor-sensitive mutant infection of Bacillus subtilis.

Phage phi29 suppressor-sensitive (sus) mutants of 14 cistrons have been examined for production of (14)C-labeled viral-specific proteins in restrictive infections of Bacillus subtilis. Proteins specified by four cistrons (H, J, L, and N) have been resolved and identified by sodium dodecyl sulfate gel electrophoresis and autoradiography, and fragments of the normal polypeptides were detected. Mutants of six cistrons (C, D, E, F, I, and M) demonstrated two or more missing bands in the gel profiles, and thus some of these gene products may have regulatory functions. Mutation was detected in at least five genes coding for low-molecular-weight proteins, but a conditionally lethal mutant in only one of these genes has been isolated. Preliminary evidence that a precursor protein is cleaved to generate the neck appendage structural protein and a low-molecular-weight product has been obtained.

Amino Acids↗
PubMed1985

Graft rejection in a congenic panel of rats with defined immune response genes for class I antigens. II. Quantitative aspects of Ir gene function in a full-haplotype mismatch.

Previous studies have shown that the Ir-gene-controlled rejection of rl tissues by c/u responder and non-rejection by c low responders does not extend to tissues expressing a full a haplotype mismatch. However, antibody responses and liver graft rejection are both defective in low responders, even across a full haplotype barrier. We have therefore used a titrated adoptive transfer assay to search for quantitative differences in the responsiveness of c and c/u animals to a organ grafts. We first established that a heart graft rejection could be ablated in both recipient strains with whole-body irradiation and could be restored with syngeneic cells. Titration of restorative cells revealed that 5 times as many c cells were required to restore graft rejection in c recipients as c/u cells were required in c/u recipients. Use of cells from primed donors showed that in both c/u and c animals these cells had undergone about a 5-fold increase in potency, showing that there was no failure of proliferation and differentiation in the low responder after contact with antigens. Cross-transfer experiments were done to attempt to localize the defect in low-responder animals either to a failure of low-responder antigen-presenting cells (APC) to trigger a response or a defect in the responsiveness of alloreactive cells toward the a antigens. In these experiments c cells were obtained from radiation chimeras of the c----c/u type. These cells were used to restore graft rejection in c/u irradiated recipients. Similar experiments employing c/u cells obtained from c/u----c chimeras and given to irradiated c recipients were also done. These showed that c cells from chimeras were marginally less potent than c/u cells from chimeras. In contrast when cross-transfer of c/u cells to c animals bearing a nonrejected rl heart was done, no rejection was seen even when antigen presenting cells were cotransferred. The conclusions from this series of experiments were that quantitatively small defects were present in both repertoire and antigen presentation, and that these quantitative defects in aggregate were probably sufficient to explain the documented low responsiveness of c animals to the a haplotype. The failure of high-responder c/u cells to secure rejection of rl tissues in the low-responder c environment suggests that presentation of isolated class I differences in host APCs is mandatory for rejection to occur and is highly defective in the c animal.

Animals↗
PubMed1986

Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression.

A chimeric gene was constructed in which sequences between 2,000 base pairs upstream of the start of transcription of the mouse alpha 2(I) collagen gene and 54 base pairs downstream of this site were fused to the chloramphenicol acetyltransferase (CAT) gene. We present evidence suggesting that this collagen gene segment is sufficient for cell-specific expression of the chimeric gene. Indeed, the levels of CAT activity in transient expression experiments were at least 10 times higher after transfection of NIH 3T3 cells than after transfection of a mouse myeloma cell line, whereas much less difference was found after transfection of these two cell types with pSV2-CAT, a plasmid in which the early simian virus 40 promoter is fused to the CAT gene. Several deletions were introduced in the same 5'-flanking segment of the alpha 2(I) collagen gene, and the effects of these deletions were examined after DNA transfection of the chimeric collagen-CAT gene into NIH 3T3 cells. At least two segments broadly located between -979 and -502 and between -346 and -104 are needed for optimal expression of the chimeric gene. These results were obtained both in transient expression experiments and by analysis of pools of NIH 3T3 cells that were stably transfected with the different mutants. In general, the effects of the deletions on the activity of the alpha 2(I) collagen promoter were analogous, whether the plasmids harbored the simian virus 40 enhancer sequence or not, although the overall levels of expression of the chimeric gene were increased when the recombinant plasmids contained this sequence.

Animals↗
PubMed1972

Histocompatibility-linked immune response gene function in guinea pigs. Specific inhibition of antigen-induced lymphocyte proliferation by alloantisera.

A number of autosomal dominant immune response (IR) genes have been identified in both mice and guinea pigs. These IR genes have been shown to be linked to the major histocompatibility antigens of the species and to be functionally expressed primarily in T lymphocytes. In order to more fully understand the relationship between IR genes, histocompatibility antigens, and immune recognition, the effect of specific alloantisera on lymphocyte stimulation induced by antigens under control of IR genes was examined. Using lymphocytes from strain 2 or strain 13 animals, the in vitro proliferative responses both to antigens which are known to be under genetic control (DNP-GL in strain 2 guinea pigs and GT in strain 13 guinea pigs) and to an antigen which is not known to be under genetic control (PPD) were inhibited to a similar degree and to a much greater extent than the response to phytohemagglutinin. However, when cells from F(1) (2 x 13) animals are used, the alloantisera markedly inhibit only the response which is linked to the histocompatibility antigens against which the serum is directed. Thus, the anti-2 serum inhibited the response to DNP-GL but not to GT; the anti-13 serum inhibited the response to GT but did not affect DNP-GL response. The inhibitory activity of the alloantisera could not be removed by absorption with gamma globulin of the opposite strain. It can be concluded from these observations that immune response genes produce a cell surface-associated product and that this product plays a role in the mechanism of antigen recognition by the T lymphocyte. The mechanisms by which alloantisera block this process of antigenic recognition is not resolved nor is the relationship between the IR gene product and the antigen-binding receptor of the T lymphocyte. The approach described here offers a powerful tool for the resolution of these problems.

Animals↗
PubMed1998

Requirement for Xvent-1 and Xvent-2 gene function in dorsoventral patterning of Xenopus mesoderm.

Xvent-1 and Xvent-2 are members of a novel homeobox subfamily that have been implicated in dorsoventral patterning in Xenopus mesoderm and are thought to function in BMP signalling. Here we investigate the requirement for Xvent function by employing two dominant-negative strategies. Loss of Xvent function dorsalizes ventral mesoderm, induces secondary embryonic axes and directly neuralizes ectoderm. We further find that (1) Xvents act as transcriptional repressors, (2) Xvents function in an additive fashion and (3) a surprising number of genes are able to rescue dominant-negative Xvent phenotypes including Bmp-4, Smad-1 and wild-type Xvents and Xhox3, but not Xwnt-8. The results show that Xvent-1 and Xvent-2 are essential for ventral mesoderm formation and for preventing neural differentiation. A model is suggested to explain how Bmp-4 positional information is converted into distinct cellular responses.

Animals↗
PubMed1997

A ribozyme-mediated, gene "knockdown" strategy for the identification of gene function in zebrafish.

The zebrafish system offers many unique opportunities for the study of molecular biology. To date, only random mutagenesis, and not directed gene knockouts, have been demonstrated in this system. To more fully develop the potential of the zebrafish system, an approach to effectively inhibit the expression of any targeted gene in the developing zebrafish embryo has been developed. This approach uses a transient, cytoplasmic, T7 expression system, injected into the fertilized zebrafish egg to rapidly produce high levels of a ribozyme directed against the mRNA encoded by the targeted gene to inhibit its expression. In a demonstration of this strategy, expression of the recessive dominant zebrafish no tail gene was effectively inhibited by using this strategy to yield a phenotype identical to that resulting from a known defective mutation in this same gene. This, ribozyme-mediated, message deletion strategy may have use in determining the function of genetic coding sequences of unknown function.

Animals↗
PubMed1993

The strawberry notch gene functions with Notch in common developmental pathways.

Genetic and phenotypic analysis of strawberry notch suggests that its gene product is required during embryogenesis and oogenesis, and for the development of the eye, wing and leg. Several lines of evidence suggest that strawberry notch participates together with Notch in many common pathways. A number of strawberry notch mutant phenotypes are similar to those of Notch mutants and can be rescued by an extra copy of wild-type Notch. In addition, mutations in strawberry notch interact strongly with Notch mutants in a tissue-specific manner. Mutations in the strawberry notch and Notch loci also show very similar interactions with genes like Hairless, Delta, groucho, Serrate, and deltex that have all been proposed to participate in Notch related pathways. The genetic evidence presented here suggests that strawberry notch participates with members of the Notch pathway in facilitating developmentally relevant cell-cell communications.

Animals↗
PubMed1982

Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

These studies were stimulated by the observation, reported in the accompanying paper (19), that IEu failed to interact with I-Ak or I-As in F1 mice to allow a response to the antigen, pigeon cytochrome c, unlike I-E subregions derived from other Ia.7+ haplotypes. Serological and biochemical analyses were performed to determine whether or not cells from these F1 mice express the Ak,se:E alpha complexes that should function as restriction elements for T cell recognition of pigeon cytochrome c on antigen-presenting cells. Using the Y-17 monoclonal antibody, which recognizes the combinatorial or conformational determinant Ia.m44 on certain Ae:E alpha complexes, we were able to distinguish between Aue:Eu alpha and Ab,k,se:Eu alpha complexes on cell surfaces. Although complement-dependent microcytotoxicity with Y-17 failed to detect Ab,k,se:Eu alpha complexes on cells from appropriate F1 mice, these molecules were detected by both quantitative absorption and quantitative immunofluorescence studies. However, Ab,k,se:Eu alpha complexes were found to be present at levels only one-seventh to one-eighth the levels expressed by homozygous I-Ab, I-Ek; I-Ak, I-Ek; and I-As, I-Ek cells. The results of two-dimensional polyacrylamide gel electrophoresis analyses suggest that the low levels of expression of Ab,k,se:Eu alpha complexes are a consequence of the preferential association of Aue and Eu alpha chains with each other in the F1 cells. As will be shown in the following paper (19), the quantitative deficiency in the expression of Ake:Eu alpha and Ase:Eu alpha complexes results in a corresponding defect in antigen-presenting cell function, thus providing strong evidence that Ia antigens represent products of Ir genes.

Animals↗
PubMed1996

The rpoD gene functions as a multicopy suppressor for mutations in the chaperones, CbpA, DnaJ and DnaK, in Escherichia coli.

The CbpA protein is an analog of the DnaJ molecular chaperone of Escherichia coli. The dnaJ- cbpA- double-null mutant exhibits severe defects in cell growth, namely, a very narrow temperature range for growth. To gain insight into the functions of CbpA as well as DnaJ, we isolated a multicopy suppressor gene that permits this dnaJ- cbpA- mutant to grow normally at low temperatures. The suppressor gene was identified as rpoD, the gene that encodes the major sigma 70. The biological implications of this finding are examined and discussed.

Bacterial Proteins↗
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↗
PubMed1998

Effects of Alu insertions on gene function.

Alu elements are a family of short interspersed repetitive elements (SINEs) found exclusively in primates. These elements are around 300 base pairs long, are found in excess of one million copies per diploid genome, and are dispersed throughout the human genome. Alu elements are scattered by a mechanism called "retrotransposition". Three independent steps are involved in retrotransposition: transcription of the Alu repetitive element, reverse transcription of the Alu RNA and integration of the Alu cDNA. The fact that Alu elements retrotranspose so readily suggests that they have a myriad of effects on the genome, mostly by inactivating genes or altering their function. These characteristics of Alu repetitive elements point to these repetitive DNA fragments as a major driving force for evolution. In addition, Alu elements are known to adopt diverse functions depending on the context of the surrounding genetic material into which they insert. In this article, we review some of the evidence that demonstrates the functional significance of Alu repeats.

Alu Elements↗
PubMed1997

ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation.

ELO2 and ELO3 were identified from the Saccharomyces cerevisiae genome data base as homologues of ELO1, a gene involved in the elongation of the fatty acid 14:0 to 16:0. Mutations in these genes have previously been shown to produce pleiotropic effects involving a number of membrane functions. The simultaneous disruption of ELO2 and ELO3 has also been shown to produce synthetic lethality, indicating that they have related and/or overlapping functions. Gas chromatography and gas chromatography/mass spectroscopy analyses reveal that null mutations of ELO2 and ELO3 produce defects in the formation of very long chain fatty acids. Analysis of the null mutants indicates that these genes encode components of the membrane-bound fatty acid elongation systems that produce the 26-carbon very long chain fatty acids that are precursors for ceramide and sphingolipids. Elo2p appears to be involved in the elongation of fatty acids up to 24 carbons. It appears to have the highest affinity for substrates with chain lengths less than 22 carbons. Elo3p apparently has a broader substrate specificity and is essential for the conversion of 24-carbon acids to 26-carbon species. Disruption of either gene reduces cellular sphingolipid levels and results in the accumulation of the long chain base, phytosphingosine. Null mutations in ELO3 result in accumulation of labeled precursors into inositol phosphoceramide, with little labeling in the more complex mannosylated sphingolipids, whereas disruption of ELO2 results in reduced levels of all sphingolipids.

Acetyltransferases↗