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At least 991 records · Page 55Linked to original sources
PubMed2006

Development of NG2 neural progenitor cells requires Olig gene function.

In the adult central nervous system, two distinct populations of glial cells expressing the chondroitin sulfate proteoglycan NG2 have been described: bipolar progenitor cells and more differentiated "synantocytes." These cells have diverse neurological functions, including critical roles in synaptic transmission, repair, and regeneration. Despite their potential importance, the genetic factors that regulate NG2 cell development are poorly understood, and the relationship of synantocytes to the oligodendroglial lineage, in particular, remains controversial. Here, we show that >90% of embryonic and adult NG2 cells express Olig2, a basic helix-loop-helix transcription factor required for oligodendrocyte lineage specification. Analysis of mice lacking Olig function demonstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus. These findings show a general requirement for Olig function in NG2 cell development and highlight further roles for Olig transcription factors in neural progenitor cells.

Animals↗
PubMed1986

Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

We have isolated two genes from yeast encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase [hydroxymethylglutaryl-coenzyme A reductase (NADPH); HMG-CoA reductase; EC 1.1.1.34], the rate-limiting enzyme of sterol biosynthesis. These genes, HMG1 and HMG2, were identified by hybridization to a cDNA clone encoding hamster HMG-CoA reductase. DNA sequence analysis reveals homology between the amino acid sequence of the proteins encoded by the two yeast genes and the carboxyl-terminal half of the hamster protein. Cells containing mutant alleles of both HMG1 and HMG2 are unable to undergo spore germination and vegetative growth. However, cells containing a mutant allele of either HMG1 or HMG2 are viable but are more sensitive to compactin, a competitive inhibitor of HMG-CoA reductase, than are wild-type cells. Assays of HMG-CoA reductase activity in extracts from hmg1- and hmg2- mutants indicate that HMG1 contributes at least 83% of the activity found in wild-type cells.

Chromosome Mapping↗
PubMed1990

Isolation and characterization of the human homologue of rig and its pseudogenes: the functional gene has features characteristic of housekeeping genes.

rig (rat insulinoma gene) was first isolated from a cDNA library of rat insulinomas and has been found to be activated in various human tumors such as insulinomas, esophageal cancers, and colon cancers. Here we isolated the human homologue of rig from a genomic DNA library constructed from a human esophageal carcinoma and determined its complete nucleotide sequence. The gene is composed of about 3000 nucleotides and divided into four exons separated by three introns: exon 3 encodes the nuclear location signal and the DNA-binding domain of the RIG protein. The transcription initiation site was located at -46 base pairs upstream from the first ATG codon. The 5'-flanking region of the gene has no apparent TATA-box or CAAT-box sequence. However, two GC boxes are found at -189 and -30 base pairs upstream from the transcription initiation site and five GC boxes are also found in introns 1 and 2. The gene is bounded in the 5' region by CpG islands, regions of DNA with a high GC content and a high frequency of CpG dinucleotides relative to the bulk genome. Furthermore, the human genome contains at least six copies of RIG pseudogenes, and four of them have the characteristics of processed pseudogenes. From these results together with the finding that RIG is expressed in a wide variety of tissues and cells, we speculate that RIG belongs to the class of "housekeeping" genes, whose products are necessary for the growth of all cell types.

Adenoma, Islet Cell↗
PubMed1999

The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin.

Camptothecin is an antitumor agent that kills cells by converting DNA topoisomerase I into a DNA-damaging poison. Although camptothecin derivatives are now being used to treat tumors in a variety of clinical protocols, the cellular factors that influence sensitivity to the drug are only beginning to be understood. We report here that two genes required for sister chromatid cohesion, TRF4 and MCD1/SCC1, are also required to repair camptothecin-mediated damage to DNA. The hypersensitivity to camptothecin in the trf4 mutant does not result from elevated expression of DNA topoisomerase I. We show that Trf4 is a nuclear protein whose expression is cell cycle-regulated at a post-transcriptional level. Suppression of camptothecin hypersensitivity in the trf4 mutant by gene overexpression resulted in the isolation of three genes: another member of the TRF4 gene family, TRF5, and two genes that may influence higher order chromosome structure, ZDS1 and ZDS2. We have isolated and sequenced two human TRF4 family members, hTRF4-1 and hTRF4-2. The hTRF4-1 gene maps to chromosome 5p15, a region of frequent copy number alteration in several tumor types. The evolutionary conservation of TRF4 suggests that it may also influence mammalian cell sensitivity to camptothecin.

Amino Acid Sequence↗
PubMed2004

Identifying subtle interrelated changes in functional gene categories using continuous measures of gene expression.

MOTIVATION: Analysis of large-scale expression data is greatly facilitated by the availability of gene ontologies (GOs). Many current methods test whether sets of transcripts annotated with specific ontology terms contain an excess of 'changed' transcripts. This approach suffers from two main limitations. First, since gene expression is continuous rather than discrete, designating a gene as changed or unchanged is arbitrary and oblivious to the actual magnitude of the change. Second, by considering only the number of changed genes, finer changes in expression patterns associated with the category may be ignored. Since genes generally participate in multiple networks, widespread and subtle modifications in expression patterns are at least as important as extreme increases/decreases of a few genes. RESULTS: Numerical simulations confirm that incorporating continuous measures of gene expression for all measured transcripts yields detection of considerably more subtle changes. Applying continuous measures to microarray data from brains of mice injected with the Parkinsonian neurotoxin, MPTP, enables detection of changes in various biologically relevant GO terms, many of which are overlooked by discrete approaches.

Algorithms↗
PubMed1987

Complete nucleotide sequence of the mouse lactate dehydrogenase-A functional gene: comparison of the exon-intron organization of dehydrogenase genes.

The complete sequence of 12,851 nucleotides of the mouse lactate dehydrogenase-A (LDH-A) gene has been determined. It includes eight exons, seven introns, promoter and regulatory regions. The B1 repetitive elements present in intron III and VI are oriented in opposite orientation, and they share 72% sequence homology. The exon-intron organization of mouse LDH-A gene is compared with the organizations of other dehydrogenase genes, and the molecular evolution of the nicotinamide adenine dinucleotide binding domains is discussed.

Animals↗
PubMed2002

Conservation of gene function in the solanaceae as revealed by comparative mapping of domestication traits in eggplant.

Quantitative trait loci (QTL) for domestication-related traits were identified in an interspecific F(2) population of eggplant (Solanum linnaeanum x S. melongena). Although 62 quantitative trait loci (QTL) were identified in two locations, most of the dramatic phenotypic differences in fruit weight, shape, color, and plant prickliness that distinguish cultivated eggplant from its wild relative could be attributed to six loci with major effects. Comparison of the genomic locations of the eggplant fruit weight, fruit shape, and color QTL with the positions of similar loci in tomato, potato, and pepper revealed that 40% of the different loci have putative orthologous counterparts in at least one of these other crop species. Overall, the results suggest that domestication of the Solanaceae has been driven by mutations in a very limited number of target loci with major phenotypic effects, that selection pressures were exerted on the same loci despite the crops' independent domestications on different continents, and that the morphological diversity of these four crops can be explained by divergent mutations at these loci.

Chromosome Mapping↗
PubMed1985

Yeast contains two functional genes coding for ribosomal protein S10.

The DNA sequence of the second copy of the gene coding for yeast ribosomal protein S10 was determined and compared with the sequence of the first gene-copy. In addition, the sites at which the transcription of these genes start and terminate are identified. The amino acid coding regions of the two gene copies are virtually identical. The leader and in particular the trailer sequences, however, are significantly different, while the intervening sequences have hardly any homology. Taking advantage of the sequence differences we could establish that both genes are expressed in the vegetatively growing yeast cell; the respective transcripts, however, differ in their relative amounts.

Amino Acid Sequence↗
PubMed1994

Can hammerhead ribozymes be efficient tools to inactivate gene function?

In order to improve hammerhead ribozyme efficiency and specificity, we have analyzed, both in vitro and in vivo, the activity of a series of ribozyme/substrate combinations that have the same target sequence but differ in the length of the ribozyme/substrate duplex or in their structure, i.e., the total length of the RNA. In vitro, we have found that optimal kcat/Km (at 37 degrees C) is obtained when the ribozyme/substrate duplex has a length of 12 bases, which according to the base composition represents a calculated free energy of binding of -16 kcal/mol. We discuss the importance of this value for ribozyme specificity and present strategies that may improve it. Increasing the length of the duplex from 14 to 17 bases (from -19 to -26 kcal/mol) produces a reduced ribozyme activity which is probably due to a slower rate of product dissociation. In addition, inclusion of either the substrate or the ribozyme in a long transcript produces a reduction (10 fold) of the kcat/Km, probably because of a different accessibility of the target sequence. In vivo, the activity of the trans-acting ribozyme was extremely low and detected in only one case: with a ribozyme/substrate duplex length of 13 bases and with both ribozyme and substrate embedded in short RNAs expressed at a very high level. The similarity of the results obtained in vitro and in vivo indicates that it is possible to use an in vitro system to optimize ribozymes which are to be used in vivo. Satisfactory results were obtained in vivo only with cisacting ribozymes. Altogether these results suggest that the ribozyme/substrate hybridization step is the limiting step in vivo and therefore it is not clear if ribozymes represent an improvement over antisense RNAs.

Base Sequence↗
PubMed2001

Discovery of functional genes in the post-genome era by novel RNA-protein hybrid ribozymes.

Novel ribozymes were constructed that couple the site specific cleavage activity of the hammerhead ribozyme with the unwinding activity of the endogenous RNA helicase. This leads to extremely efficient cleavage of any target mRNA regardless of the secondary structure of the RNA. Since the novel hybrid ribozymes can attack any site within mRNA, libraries were made of the hybrid ribozymes with randomized binding arms and introduced into cells. This procedure made it possible to readily identify the relevant genes associated with phenotype in the apoptosis pathway. This application of a randomized library of hybrid ribozymes represents a simple powerful method for identification of genes associated with specific phenotypes.

Genes↗