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At least 613 records · Page 34Linked to original sources
PubMed2002

Transdifferentiation and nuclear reprogramming in hematopoietic development and neoplasia.

Cell transplantation and tissue regeneration studies indicate a surprisingly broad developmental potential for lineage-committed hematopoietic stem cells (HSCs). Under these conditions HSCs transition into myocytes, neurons, hepatocytes or other types of nonhematopoietic effector cells. Equally impressive is the progression of committed neuronal stem cells (NSCs) to functional blood elements. Although critical cell-of-origin issues remain unresolved, the possibility of lineage switching is strengthened by a few well-controlled examples of cell-type conversion. At the molecular level, switching probably initiates from environmental signals that induce epigenetic modifications, resulting in changes in chromatin configuration. In turn, these changes affect patterns of gene expression that mediate divergent developmental programs. This review examines recent findings in nuclear reprogramming and cell fusion as potential causative mechanisms for transdifferentiation during normal and malignant hematopoiesis.

Animals↗
PubMed1995

Analysis of the chicken GPAT/AIRC bidirectional promoter for de novo purine nucleotide synthesis.

GPAT and AIRC encode two enzymes that catalyze steps 1 and 6 plus 7, respectively, of the de novo purine biosynthetic pathway. The chicken genes are closely linked and divergently transcribed from an approximately 230-base pair intergenic region. The promoter was scanned by deletion mutagenesis in a bireporter vector that allowed assay of transcriptional activity in both directions in transfected HepG2 and chicken LMH cells. Three classes of deletions were obtained: those affecting bidirectional transcription, those predominantly affecting GPAT transcription, and those predominantly affecting AIRC transcription. Defects in bidirectional transcription resulted from removal of an initiator-like element overlapping the AIRC transcription start site, as well as deletions removing a series of GC and CCAAT boxes from the AIRC proximal half of the promoter and a CCAAT-containing segment from the GPAT side. Several regions in the GPAT proximal half of the promoter, including an octamer-like motif downstream from the transcription start site, were required predominantly for GPAT expression. Evidence for interaction of HeLa nuclear proteins with some of these sites was obtained by gel retardation, DNase I, and methylation interference assays. Overall, the results showed that the intergenic region is an integrated bidirectional promoter and that a novel initiator-like element plays a central role in coordinating expression of the divergently transcribed AIRC and GPAT genes.

Amidophosphoribosyltransferase↗
PubMed1986

Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events.

The rabbit kappa light chain gene family is characterized by the presence of two constant region (C kappa) genes; the C kappa 1 gene encodes the constant region of the principal rabbit immunoglobulin light chain, the C kappa 2 gene being not or very poorly expressed in domestic rabbits. There exist four major K1 alleles (b4, b5, b6, and b9), which are unequally expressed in heterozygous rabbits at the K1 locus. Here, we compare the nucleotide sequences of the joining (J) clusters of the kappa light chain gene (J kappa) linked to the b4K2 locus and to the b4 and b9 alleles at the K1 locus. As for C kappa genes, there is evidence for intergenic conversion between the J kappa 1 and J kappa 2 clusters as well as maximum divergence in the expressed J segments. The b9 J kappa 1 cluster differs from its b4 counterpart in that two out of the five J kappa segments (J1 and J2) are expressed instead of only one. This implies that preferential expression of the b4 allele as compared to the b9 allele is not only correlated to the number of available J kappa pieces. The b9 J2 segment is functional in spite of the presence of a termination codon immediately upstream of its coding region. Two major structural differences were observed between the J-C intron sequences of the b9 and b4 alleles; namely a 160-base-pair deletion of an A + T-rich sequence in b9 (which also occurs in the K2 locus) and a 10-base-pair deletion plus some substitutions in the region corresponding to the mouse kappa intron activating element. These differences could underlie the lower transcriptional rate of the b9 allele.

Alleles↗
PubMed1997

The acid lipase gene family: three enzymes, one highly conserved gene structure.

Human gastric lipase (HGL; triacylglycerol lipase; EC 3.1.1.3) plays an important role in the digestion of dietary triglycerides in the gastrointestinal tract, especially in patients suffering from pancreatic lipase deficiencies. The enzyme is secreted by the fundic mucosa of the stomach and hydrolyzes the ester bonds of triglycerides under acidic pH conditions, while cholesteryl esters are not attacked. The 379-amino acid protein is highly homologous to two other acidic lipases, rat lingual lipase (RLL; triacylglycerol lipase; EC 3.1.1.3) and human lysosomal acid lipase (HLAL; cholesteryl esterase; EC 3.1.1.13). To determine whether this remarkable similarity is also present at the genomic level, we have elucidated the respective gene structures by screening three bacteriophage lambda libraries and by polymerase chain reaction-based intron amplification. The genes encoding HGL, RLL, and HLAL are composed of 10 exons interrupted by nine introns and span about 14 kb, 18.7 kb, and 38.8 kb of genomic DNA, respectively. The HGL and RLL gene organizations are identical, suggesting that RLL is the rat gastric lipase expressed in the serous von Ebner glands of the tongue. The positions of the HLAL intervening sequences are also absolutely conserved, except for the location of intron 1. Our results support the concept that HLAL and HGL/RLL are members of a gene family of lipases that most likely have evolved by duplication of an ancestral gene and subsequently assumed distinct roles in neutral lipid metabolism due to sequence divergence and different expression patterns.

Animals↗
PubMed2006

Time-resolved determination of the CcpA regulon of Lactococcus lactis subsp. cremoris MG1363.

Carbon catabolite control protein A (CcpA) is the main regulator involved in carbon catabolite repression in gram-positive bacteria. Time series gene expression analyses of Lactococcus lactis MG1363 and L. lactis MG1363DeltaccpA using DNA microarrays were used to define the CcpA regulon of L. lactis. Based on a comparison of the transcriptome data with putative CcpA binding motifs (cre sites) in promoter sequences in the genome of L. lactis, 82 direct targets of CcpA were predicted. The main differences in time-dependent expression of CcpA-regulated genes were differences between the exponential and transition growth phases. Large effects were observed for carbon and nitrogen metabolic genes in the exponential growth phase. Effects on nucleotide metabolism genes were observed primarily in the transition phase. Analysis of the positions of putative cre sites revealed that there is a link between either repression or activation and the location of the cre site within the promoter region. Activation was observed when putative cre sites were located upstream of the hexameric -35 sequence at an average position of -56.5 or further upstream with decrements of 10.5 bp. Repression was observed when the cre site was located in or downstream of putative -35 and -10 sequences. The highest level of repression was observed when the cre site was present at a defined side of the DNA helix relative to the canonical -10 sequence. Gel retardation experiments, Northern blotting, and enzyme assays showed that CcpA represses its own expression and activates the expression of the divergently oriented prolidase-encoding pepQ gene, which constitutes a link between regulation of carbon metabolism and regulation of nitrogen metabolism.

Bacterial Proteins↗
PubMed2004

Genome scanning for interspecific differentiation between two closely related oak species [Quercus robur L. and Q. petraea (Matt.) Liebl.].

Interspecific differentiation values (G(ST)) between two closely related oak species (Quercus petraea and Q. robur) were compiled across different studies with the aim to explore the distribution of differentiation at the genome level. The study was based on a total set of 389 markers (isozymes, AFLPs, SCARs, microsatellites, and SNPs) for which allelic frequencies were estimated in pairs of populations sampled throughout the sympatric distribution of the two species. The overall distribution of G(ST) values followed an L-shaped curve with most markers exhibiting low species differentiation (G(ST) < 0.01) and only a few loci reaching >10% levels. Twelve percent of the loci exhibited significant G(ST) deviations to neutral expectations, suggesting that selection contributed to species divergence. Coding regions expressed higher differentiation than noncoding regions. Among the 389 markers, 158 could be mapped on the 12 linkage groups of the existing Q. robur genetic map. Outlier loci with large G(ST) values were distributed over 9 linkage groups. One cluster of three outlier loci was found within 0.51 cM; but significant autocorrelation of G(ST) was observed at distances <2 cM. The size and distribution of genomic regions involved in species divergence are discussed in reference to hitchhiking effects and disruptive selection.

Crosses, Genetic↗
PubMed1995

Medium-dependent regulation of proteinase gene expression in Lactococcus lactis: control of transcription initiation by specific dipeptides.

Transcriptional gene fusions with the Escherichia coli beta-glucuronidase gene (gusA) were used to study the medium- and growth-dependent expression of the divergently transcribed genes involved in proteinase production (prtP and prtM) of Lactococcus lactis SK11. The results show that both the prtP and prtM genes are controlled at the transcriptional level by the peptide content of the medium and, to a lesser extent, by the growth rate. A more than 10-fold regulation in beta-glucuronidase activity was observed for both prtP and prtM promoters in batch and continuous cultures. The level of expression of the prtP and prtM promoters was high in whey permeate medium with relatively low concentrations of peptides, whereas at increased concentrations the expression of the promoters was repressed. The lowest level of expression was observed in peptide- and amino acid-rich laboratory media, such as glucose-M17 and MRS. The addition of specific dipeptides, such as leucylproline and prolylleucine, to the growth medium negatively affected the expression of the prtP-gusA fusions. The repression by dipeptides was not observed in mutants defective in the uptake of di-tripeptides, indicating that the internal concentration of dipeptides or derivatives is important in the regulation of proteinase production.

Bacterial Proteins↗
PubMed2002

[Genetic divergence of Far Eastern dace species belonging to the genus Tribolodon (Pisces, Cyprinidae) and closely related taxa].

Based on a biochemical-genetic approach, heterozygosity and divergence of structural genes of 30 enzyme loci were analyzed in six dace species. In addition, intra- and interspecific divergence of gene expression was analyzed based on a sample of 12 to 15 loci. Mean heterozygosities per individual varied as follows: Tribolodon species, Hobs = 0.007 +/- 0.007 and Hexp = 0.007 +/- 0.007; T. ezoe, Hobs = 0.045 +/- 0.016 and Hexp = 0.067 +/- 0.029. Several variants of genetic distances were estimated. Standard Nei's distances (DN) varied from 0.145 to 0.284 in four dace species studied. As related to Tribolodon dace species, the following genetic distances were obtained for two members of other genera: Pseudaspius leptocephalus, DN = 0.269; Leuciscus waleckii, DN = 0.769. Based on the distance matrices, different clustering algorithms were realized. The main feature shared by different dendrograms was a separate position of the cluster joining Far-Eastern dace species, to which P. leptocephalus and L. waleckii are successively added. Among the species studied, the proportion of loci similar by expression (E) varied from 87 to 100%. The greatest difference was found between anadromous and nonanadromous ecotypes of T. hakonensis, E = 67%. The following conclusions can be made: (1) Four studied species of the genus Tribolodon are rather well genetically differentiated. Diagnostic loci are available. (2) A nominal dace species, T. species, should be considered the fourth isolated species of this genus, which is confirmed by its recent zoological acceptance of this species. (3) The origin and divergence of dace species belonging to the genus Tribolodon are relatively late (1 to 3 Myr ago) historical events. (4) Taxonomically, the genus Tribolodon belong to the tribe Pseudaspinini together with P. leptocephalus, which is confirmed by genetic data. (5) Data on heterozygosity and the divergence of structural and regulatory elements of genome, along with the proposed scheme of speciation types, suggest the following speciation modes for the species studied: for four species, adaptive divergence and for two species, genetic transformation.

Animals↗
PubMed1995

Divergent transcription and a remote operator play a role in control of expression of a nopaline catabolism promoter in Agrobacterium tumefaciens.

The nocP-nocR divergent gene arrangement of the nopaline catabolism (noc) operon of the Agrobacterium tumefaciens Ti plasmid pTiT37 was examined with respect to the expression of the nocP promoter. Under repressive conditions, i.e. in the absence of nopaline, four distinct levels of PnocP expression were observed. The lowest level of expression, i.e. full repression, was detected in the presence of the NocR repressor, together with the remote noc operator and productive transcription from the divergent nocR promoter. The next level was observed in the absence of either the NocR protein or of the operator or of both. The third level was detected when abortive transcription from the nocR promoter occurred, irrespective of the presence or absence of the NocR protein. The highest level of PnocP expression was observed in the absence of both productive transcription from PnocR and the operator sequence, whether or not the NocR protein was present. Under inductive conditions, i.e. in the presence of nopaline, expression of PnocP was activated if both the NocR protein and the operator were present. Absence of either NocR or the operator resulted in lack of inducibility of the nocP promoter. Transcription from the divergent nocR promoter had no influence on the activation of PnocP. It was also found that the absence of the operator affected plasmid supercoiling in vivo. The results suggest that DNA topology has a role in the regulation of the nocP promoter.

Agrobacterium tumefaciens↗
PubMed1989

Novel cis-acting elements in Petunia Cab gene promoters.

In order to identify specific cis-acting elements which regulate the expression of the divergent Cab22R and Cab22L genes of Petunia, we conducted systematic mutational studies of the 1 kb intergenic promoter region. Sequence analysis revealed three GATA box sequence repeats positioned between the TATA and CAAT box elements. These GATA elements are conserved in corresponding promoter regions of all LHCII Type I Cab genes in Petunia and other dicotyledonous plants we have examined. Site-specific mutations in the CAAT box and the GATA box elements of the Cab22R promoter resulted in 8-fold and 5-fold reductions in Cab22R transcript levels respectively. A deletion of 52 bp, adjacent and upstream from the CAAT box (-92 to -145) in the Cab22R promoter reduced transcript levels 20-fold. This deletion contains a region of 13 bp which is conserved between many Petunia Cab genes. These results indicate that the quantitative expression of the Cab22 promoters is regulated by multiple cis-acting elements including CAAT and GATA box elements as well as sequences located between -92 and -145. The deletion of the region between -92 and -145 is partially compensated by homologous sequences present in the adjacent divergent promoter Cab22L.

Base Sequence↗
PubMed2001

Casitone-mediated expression of the prtP and prtM genes in Lactococcus lactis subsp. lactis BGIS29.

Casitone added to chemically defined medium (CDM) specifically influenced the regulation of the proteinase activity in the natural isolate Lactococcus lactis subsp. lactis BGIS29. Comparative analysis of the influence of casitone present in CDM on the proteolytic activity of strain BGIS29 and of L. lactis subsp. cremoris strains SK11 and Wg2 indicated that the proteolytic activity of strains BGIS29 and SK11 is casitone-dependent, whereas that of strain Wg2 is not. The regulatory region of the prt genes of strain BGIS29 was cloned and sequenced. The nucleotide sequence of the prt regulatory region of strain BGIS29 was distinctly different from that of L. lactis subsp. cremoris strains SK11 and Wg2. Transcriptional gene fusions with the Escherichia coli beta-glucuronidase gene ( gusA) were used to study medium-dependent expression of two divergent prtP and prtM promoters of strain BGIS29 (designated P (prtP) and P (prtM), respectively). beta-Glucuronidase assays and Northern blot analysis showed that the activities of P (prtP) and P (prtM) are controlled by casitone at the transcriptional level.

Amino Acid Sequence↗
PubMed1997

Mutual control of the PecS/PecM couple, two proteins regulating virulence-factor synthesis in Erwinia chrysanthemi.

The Erwinia chrysanthemi pecS mutant displays constitutive production of virulence factors, such as pectinases or cellulases. Complementation of the pecS mutation can be obtained in the presence of the pecS wild-type gene on a low-copy-number plasmid. Moreover, the resulting plasmid decreases the expression of a pecS::uidA chromosomal fusion, indicating the existence of an autoregulation mechanism. This negative autoregulation was confirmed and quantified by analysis of the pecS transcripts using primer-extension experiments. Band-shift assays and DNase I footprinting experiments demonstrated that the PecS protein could bind to the intergenic regulatory region, located between the pecS and pecM genes, with a relatively high affinity (apparent dissociation constant (K'[d]) close to 4nM). These PecS-binding sites overlap the pecS and pecM promoters. The comparison of these new PecS-binding sites with those previously characterized on the target genes confirms the absence of a consensus. This observation was in accordance with the results of the missing-contact experiments performed on the pecS-pecM intergenic regulatory region and the celZ operator. Concurrently, we demonstrated that the PecS protein negatively controls the expression of the divergently transcribed pecM gene located 400bp upstream from the pecS gene. By following the efficiency of pecS autoregulation in a double E. chrysanthemi pecM-pecS mutant, we established that the PecM protein potentiates PecS activity in vivo.

Bacterial Proteins↗
PubMed2001

Expression of transcription factors during oligodendroglial development.

Transcription factors coordinate the orderly changes of gene expression that underlie all developmental processes including those of oligodendrocytes. In comparison to other systems, relatively little is known about the role of transcription factors during oligodendrocyte development. However, recent years have seen the identification of oligodendroglial transcription factors that, not surprisingly, belong to the same gene families that are also important in other tissues or cell lineages. Some transcription factors such as the bHLH (basic helix-loop-helix) proteins Olig-1 and Olig-2 or the high-mobility-group protein Sox10 are expressed already early during development of the oligodendrocyte lineage, whereas expression of other transcription factors such as the homeodomain protein Gtx/Nkx6.2 only start at the time of terminal differentiation. Once turned on, expression of these proteins can either be permanent as in the above-mentioned cases or transient as exemplified by the POU domain proteins Tst-1/Oct6/SCIP, Brn-1 and Brn-2. Analyses of these transcription factors has already led to the identification of important principles such as functional redundancy between co-expressed proteins, unexpected divergence in the transcription factor repertoire of oligodendrocytes and Schwann cells, and equally unsuspected similarities in transcription factor usage between oligodendrocytes and neurons. Although so far only a small percentage of oligodendroglial transcription factors has been identified, these are excellent candidates for regulators of cell type specification, lineage progression, and terminal differentiation.

Animals↗
PubMed2003

Organic anion-transporting polypeptide (OATP) transporter family and drug disposition.

Drug transporters are increasingly recognized as a key determinant of drug disposition. Recent studies have revealed that targeted expression of drug uptake and efflux transporters to specific cell membrane domains allows for the efficient directional movement of many drugs in clinical use. While the role of certain efflux transporters such as MDR1 (P-glycoprotein) in drug disposition has been extensively studied, emerging evidence suggests that uptake transporters may also be important to the intestinal absorption and renal or hepatic elimination of drugs. Members of the organic anion-transporting polypeptide (OATP) family of drug uptake transporters have been found capable of transporting a large array of structurally divergent drugs. Moreover, expression of OATP isoforms in the gastrointestinal tract, liver and kidney, as well as at the level of the blood-brain barrier, has important implications for our understanding of the factors governing drug absorption, elimination and tissue penetration.

Animals↗
PubMed1990

Nucleotide sequence of the gene encoding the repressor for the histidine utilization genes of Pseudomonas putida.

The hutC gene of Pseudomonas putida encodes a repressor which, in combination with the inducer urocanate, regulates expression of the five structural genes necessary for conversion of histidine to glutamate, ammonia, and formate. The nucleotide sequence of the hutC region was determined and found to contain two open reading frames which overlapped by one nucleotide. The first open reading frame (ORF1) appeared to encode a 27,648-dalton protein of 248 amino acids whose sequence strongly resembled that of the hut repressor of Klebsiella aerogenes (A. Schwacha and R. A. Bender, J. Bacteriol. 172:5477-5481, 1990) and contained a helix-turn-helix motif that could be involved in operator binding. The gene was preceded by a sequence which was nearly identical to that of the operator site located upstream of hutU which controls transcription of the hutUHIG genes. The operator near hutC would presumably allow the hut repressor to regulate its own synthesis as well as the expression of the divergent hutF gene. A second open reading frame (ORF2) would encode a 21,155-dalton protein, but because this region could be deleted with only a slight effect on repressor activity, it is not likely to be involved in repressor function or structure.

Amino Acid Sequence↗
PubMed1996

A novel human homologue of yeast nucleosome assembly protein, 65 kb centromeric to the p57KIP2 gene, is biallelically expressed in fetal and adult tissues.

Three genes on 11p15.5 are known to undergo genomic imprinting. The gene for insulin-like growth factor II (IGF2) is normally expressed from the paternal allele, while H19 and p57KIP2, a cyclin-dependent kinase inhibitor, are expressed from the maternal allele. Five germline balanced chromosomal rearrangement breakpoints from patients with Beckwith-Wiedemann syndrome (BWS) have been mapped to 11p15.5 between p57KIP2 and IGF2, and all are derived from the maternal chromosome. By positional cloning from BWS breakpoints, we have isolated a gene 100 kb and 65 kb centromeric to the proximal end of this BWS breakpoint cluster and p57KIP2, respectively. This gene is homologous to yeast nucleosome assembly protein (NAP1) and to a human homologue of NAP1, and we designate it hNAP2 (human nucleosome assembly protein 2). hNAP2 diverges in its expression pattern from IGF2, H19, and p57KIP2, and it shows biallelic expression in all tissues tested. Thus, hNAP2 is functionally insulated from the imprinting domain of 11p15.

Adult↗
PubMed1985

Rhizobium meliloti nodulation genes: identification of nodDABC gene products, purification of nodA protein, and expression of nodA in Rhizobium meliloti.

A set of conserved, or common, bacterial nodulation (nod) loci is required for host plant infection by Rhizobium meliloti and other Rhizobium species. Four such genes, nodDABC, have been indicated in R. meliloti 1021 by genetic analysis and DNA sequencing. An essential step toward understanding the function of these genes is to characterize their protein products. We used in vitro and maxicell Escherichia coli expression systems, together with gel electrophoresis and autoradiography, to detect proteins encoded by nodDABC. We facilitated expression of genes on these DNA fragments by inserting them downstream of the Salmonella typhimurium trp promoter, both in colE1 and incP plasmid-based vectors. Use of the incP trp promoter plasmid allowed overexpression of a nodABC gene fragment in R. meliloti. We found that nodA encodes a protein of 21 kilodaltons (kDa), and nodB encodes one of 28 kDa; the nodC product appears as two polypeptide bands at 44 and 45 kDa. Expression of the divergently read nodD yields a single polypeptide of 33 kDa. Whether these represent true Rhizobium gene products must be demonstrated by correlating these proteins with genetically defined Rhizobium loci. We purified the 21-kDa putative nodA protein product by gel electrophoresis, selective precipitation, and ion-exchange chromatography and generated antiserum to the purified gene product. This permitted the immunological demonstration that the 21-kDa protein is present in wild-type cells and in nodB- or nodC-defective strains, but is absent from nodA::Tn5 mutants, which confirms that the product expressed in E. coli is identical to that produced by R. meliloti nodA. Using antisera detection, we found that the level of nodA protein is increased by exposure of R. meliloti cells to plant exudate, indicating regulation of the bacterial nod genes by the plant host.

Bacterial Proteins↗
PubMed2006

Nm23-H1: a metastasis-associated gene.

The protein product of nm23-H1 gene has activity of nucleoside diphosphate (NDP) kinase, which catalyzes the phosphorylation of nucleoside diphosphates to the corresponding nucleoside triphosphates. Reductions in nm23 expression have been significantly associated with aggressive behavior in melanoma, breast, colon, and gastric carcinomas. On the contrary, high levels of nm23 gene expression are noted in the advanced stage of thyroid carcinomas and associated with significant reductions in survival for neuroblastoma and osteosarcoma patients. Although expression of nm23/NDP kinase is divergent in various malignant tumors, its reduced expression seems to be related to increased metastatic potential in most carcinoma types. However, it is hypothesized that nm23 may play a tissue-specific role, and that different regulatory mechanisms may act in different tumors. In ovarian carcinoma, nm23-H1/NDP kinase may be correlated with some clinicopathologic characteristics. In cervical cancer, nm23-H1 is probably involved in cervical carcinogenesis and correlated with some aggressive parameters. Overexpression of nm23-H1 protein may indicate poor survival for cervical cancer patients. Other than histidine 118 residue (amino acid sequence 118: histidine) concerned with NDP kinase activity of nm23-H1, serine 120 (amino acid sequence 120: serine) related activity of histidine-dependent protein phosphotransfer was recently reported to be responsible for its biological suppressive effects. To inhibit metastatic potential, nm23-H1 is also demonstrated to co-immunoprecipitate the kinase suppressor of Ras and phosphorylate it, and therefore reduce activation of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway in response to signaling.

Female↗