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At least 1,135 records · Page 63Linked to original sources
PubMed1997

Ultrabithorax and Antennapedia 5' untranslated regions promote developmentally regulated internal translation initiation.

The 5' untranslated regions (UTRs) of the Drosophila Ubx and Antp genes were tested for their ability to promote cap-independent translation initiation. The Ubx and the Antp 5' UTR were inserted between the CAT and lacZ coding sequences in a dicistronic gene and tested for IRES activity in transgenic Drosophila. Northern analysis of the mRNAs showed the presence of the predicted full-length dicistronic mRNAs. High CAT activity was expressed from the first cistron from all of the dicistronic constructs introduced into the fly genome. The dicistronic transgenic strains bearing the Ubx and Antp IRES elements expressed significant levels of beta-galactosidase (betaGAL) from the second cistron whereas little or no betaGAL was expressed in the controls lacking the IRESs. In situ analysis of betaGAL expression in the transgenic strains indicates that expression of the second cistron is spatially and temporally regulated. Although the developmental patterns of expression directed by the Antp and Ubx IRESs overlap, they exhibit several differences indicating that these IRESs are not functionally equivalent.

Animals↗
PubMed1997

Evidence for cell cycle-specific, spindle pole body-mediated, nuclear positioning in the fission yeast Schizosaccharomyces pombe.

Specific changes in spatial order occur during cell cycle progression in fission yeast. Growth of the rod-shaped cells is highly regulated and undergoes a cell cycle and size-regulated switch from monopolar to bipolar tip extension. During both phases of growth, the interphase nucleus is maintained in a central location. Following the separation of the genome to the cell tips in mitosis, the two nuclei migrate back towards the cell equator before stopping in two new positions that will become the middle of the two new cells. Here we use simultaneous labeling of microtubules, chromatin and spindle pole bodies in wild-type and cdc mutants, to show that nuclear positioning is achieved by regulation of spindle pole body-mediated nuclear migration. We show that the number and location of nuclear positioning signals is regulated in a cell cycle-specific manner and that spindle pole body-mediated forces are likely to be responsible for maintaining correct nuclear position once the nuclei have reached the appropriate position in the cell. Accentuating the movement of the nuclei back towards the cell equator after mitosis by artificially increasing cell length shows that the spindle pole body leads the nucleus during this migration. When multiple spindle pole bodies are associated with the same or different nuclei they all go to the same point indicating that the different spindle pole bodies are responding to the same positional cue. In a septation-defective mutant cell, which contains four nuclei, the spindle pole bodies on the four different nuclei initially group as two pairs in regions that would become the middle of the new cells, were the cell able to divide. In the subsequent interphase, the nuclei aggregate as a group of four in the centre of the cell. The presence of two or three clusters of spindle pole bodies in larger cells with eight nuclei suggests that the mechanisms specifying the normally central location for multiple nuclei may be unable to operate properly as the cells get larger. Perturbation of microtubules with the microtubule poison thiabendazole prevents the spindle pole body clustering in septation mutants, demonstrating that nuclear positioning requires a functional microtubule cytoskeleton.

Anaphase↗
PubMed1984

Three-dimensional intranuclear DNA organization in situ: three states of condensation and their redistribution as a function of nuclear size near the G1-S border in HeLa S-3 cells.

Characteristic variations in nuclear morphology occurring with variations in the physiological state of the cell have been observed in a number of systems to date. In this paper, we have critically examined the relationship between nuclear morphology and intranuclear DNA organization near the G1-S transition in HeLa S-3 cells, by the study of both the spatial distribution of optical density values and the optical density histograms for individual Feulgen-stained nuclei. Our results demonstrate that the majority of the DNA is located in a narrow shell surrounding the nuclear and nucleolar borders, and present evidence for at least three discrete states of chromatin condensation. Greater than 90% of the genome appears distributed among the two classes with larger density, and a redistribution between these two classes occurs as a function of changing nuclear size. Numerical simulations indicate that the observed distribution does not arise as an artifact related to overlapping but, in fact, actually represents discrete states of condensation. Interestingly, the extrapolated nuclear area at which the fraction of DNA in the state of highest density is reduced to zero, corresponds closely to the nuclear size shown elsewhere as representing the critical size that HeLa S-3 nuclei must exceed in order to initiate S phase.

Cell Nucleus↗
PubMed1998

Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.

Genomic cloning and sequencing of a human homologue (the gene name, endonuclease III-like 1; gene symbol, NTHL1 or NTH1) for Escherichia coli endonuclease III, that is involved in pyrimidine base excision repair, were performed. The sequence covered the entire NTHL1 gene consisting of six exons and five introns spanning 8kb with 5' flanking (8kb) and 3' flanking (3.8kb) regions. Southern blot analysis suggested that the NTHL1 gene exists as a single copy in a haploid genome. The sequenced 5' flanking region lacks typical TATA and CAAT boxes, but contains a CpG island having putative binding sites for several transcription factors such as Ets1 and Sp1. The NTHL1 gene lies immediately adjacent to the tuberous sclerosis 2 (TSC2) gene on chromosome 16p13.3 in a 5'-to-5' orientation. Transcription initiation sites of both NTHL1 and TSC2 genes were suggested to be multiple by 5' RACE experiments. The northern hybridization experiment suggested that both genes are expressed in all tissues, but at different levels. Downstream of the NTHL1 gene, the gene for the regulatory factor 2 (SLC9A3R2/E3KARP; also called OCTS2, TKA-1 and SIP-1) of the solute carrier family 9 (sodium/hydrogen exchanger), isoform A3, lies in a 3'-to-3' orientation. This paper demonstrates for the first time the spatial relationship of these three genes (TSC2, NTHL1 and SLC9A3R2) at the nucleotide level, and the presence of multiple transcription initiation sites of the NTHL1 and TSC2 genes.

Base Sequence↗
PubMed1998

Murine Hoxc-9 gene contains a structurally and functionally conserved enhancer.

Reporter gene analysis of the Hoxc-9 genomic region in transgenic mice allowed us to identify a positional enhancer in the Hoxc-9 intron that drives expression in the posterior neural tube of midgestation mouse embryos in a Hoxc-9-related manner. Sequence comparison to the chicken Choxc-9 intron revealed the existence of two highly conserved sequence elements (CSEs) in a similar spatial arrangement. These structural similarities in the mammalian and avian lineage are mirrored by conserved function of the chicken Choxc-9 intron in transgenic mice. Deletion analysis of the two introns suggests that full activity of both enhancers depends on cooperation between the two CSEs located close to the respective 5' and 3' splice sites. Following the paradigm of phylogenetically conserved developmental control mechanisms, the Hoxc-9 intragenic enhancer was tested in Drosophila. Our data show that the mouse Hoxc-9 enhancer acts in a conserved fashion in transgenic flies, conferring posteriorly restricted reporter gene expression to the developing central nervous system in third instar larvae. This finding indicates that the Hoxc-9 intragenic enhancer is involved in transcriptional regulatory circuits conserved between vertebrates and arthropods.

Animals↗
PubMed1985

The regulatory domain of a larval serum protein gene in Drosophila melanogaster.

DNAse I hypersensitive sites have been shown to be present at the 5' end of each of the larval serum protein genes (LSPs) when they are expressed in the fat body. They are absent from the same inactive genes in embryos. A 4.4-kb genomic fragment containing the coding region for LSP 1 alpha and 1.5 kb of 5'-flanking sequence has been reintroduced into the germ line of a strain containing an electrophoretic variant form of the alpha gene. The expression of the reintegrated gene is normal with respect to the amount of protein produced and the temporal and spatial distribution of the transcript. A comparison has been made of the chromatin configuration of the reintroduced and endogenous alpha genes and the same pattern of DNase I hypersensitivity is found. The hypersensitive regions have been located on the 5' sequence of the LSP 1 alpha gene and their sequences compared with known hypersensitive regions of other genes.

Journal Article↗
PubMed2005

Gene duplication, gene loss and evolution of expression domains in the vertebrate nuclear receptor NR5A (Ftz-F1) family.

Fushi tarazu factor 1 (Ftz-F1, NR5A) is a zinc-finger transcription factor that belongs to the nuclear receptor superfamily and regulates genes that are involved in sterol and steroid metabolism in gonads, adrenals, liver and other tissues. To understand the evolutionary origins and developmental genetic relationships of the Ftz-F1 genes, we have cloned four homologous Ftz-f1 genes in zebrafish, called ff1a, ff1b, ff1c and ff1d. These four genes have different temporal and spatial expression patterns during development, indicating that they have distinct mechanisms of genetic regulation. Among them, the ff1a expression pattern is similar to mammalian Nr5a2, while the ff1b pattern is similar to that of mammalian Nr5a1. Genetic mapping experiments show that these four ff1 genes are located on chromosome segments conserved between the zebrafish and human genomes, indicating a common ancestral origin. Phylogenetic and conserved synteny analysis show that ff1a is the orthologue of NR5A2, and that ff1b and ff1d genes are co-orthologues of NR5A1 that arose by a gene-duplication event, probably a whole-genome duplication, in the ray-fin lineage, and each gene is located next to an NR6A1 co-orthologue as in humans, showing that the tandem duplication occurred before the divergence of human and zebrafish lineages. ff1c does not have a mammalian counterpart. Thus we have characterized the phylogenetic relationships, expression patterns and chromosomal locations of these Ftz-F1 genes, and have demonstrated their identities as NR5A genes in relation to the orthologous genes in other species.

Animals↗
PubMed2001

Restoring the phenotype of fragile X syndrome: insight from the mouse model.

A mouse model for the fragile X syndrome, the most common form of inherited mental retardation, was generated a number of years ago. It shows characteristics compatible with the clinical symptoms of human patients. These include pathological changes such as macroorchidism, behavioral problems, and diminished visuo-spatial abilities. To investigate whether the fragile X syndrome is a potentially correctable disorder, several groups attempted to 'rescue' the knockout mutation by introduction of an intact copy of the FMR1 gene in the knockout mouse. Two different types of rescue mice have been created by injection of constructs based on FMR1 cDNA or on FMR1 genomic DNA. Several pathological, behavioral and cognitive function tests were performed on these two different rescue mouse lines to compare their characteristics with those of the knockout and control littermates. Each rescue line resembled the control in some aspects though neither of the 2 lines was a full 'rescue', e.g. resemble the control in all aspects investigated. Thus, rescue of some aspects of the phenotype has been achieved by introduction of FMR1 constructs in the fragile X knockout mice. The results implicate that, even if FMR1 production is cell type specific, the quantity of the FMRP expression is highly critical as overproduction may have a harmful effect.

Animals↗
PubMed2006

Widespread discordance of gene trees with species tree in Drosophila: evidence for incomplete lineage sorting.

The phylogenetic relationship of the now fully sequenced species Drosophila erecta and D. yakuba with respect to the D. melanogaster species complex has been a subject of controversy. All three possible groupings of the species have been reported in the past, though recent multi-gene studies suggest that D. erecta and D. yakuba are sister species. Using the whole genomes of each of these species as well as the four other fully sequenced species in the subgenus Sophophora, we set out to investigate the placement of D. erecta and D. yakuba in the D. melanogaster species group and to understand the cause of the past incongruence. Though we find that the phylogeny grouping D. erecta and D. yakuba together is the best supported, we also find widespread incongruence in nucleotide and amino acid substitutions, insertions and deletions, and gene trees. The time inferred to span the two key speciation events is short enough that under the coalescent model, the incongruence could be the result of incomplete lineage sorting. Consistent with the lineage-sorting hypothesis, substitutions supporting the same tree were spatially clustered. Support for the different trees was found to be linked to recombination such that adjacent genes support the same tree most often in regions of low recombination and substitutions supporting the same tree are most enriched roughly on the same scale as linkage disequilibrium, also consistent with lineage sorting. The incongruence was found to be statistically significant and robust to model and species choice. No systematic biases were found. We conclude that phylogenetic incongruence in the D. melanogaster species complex is the result, at least in part, of incomplete lineage sorting. Incomplete lineage sorting will likely cause phylogenetic incongruence in many comparative genomics datasets. Methods to infer the correct species tree, the history of every base in the genome, and comparative methods that control for and/or utilize this information will be valuable advancements for the field of comparative genomics.

Animals↗
PubMed2002

Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in cholera-endemic areas of Bangladesh.

Diversity, relatedness, and ecological interactions of toxigenic Vibrio cholerae O1 populations in two distinctive habitats, the human intestine and the aquatic environment, were analyzed. Twenty environmental isolates and 42 clinical isolates were selected for study by matching serotype, geographic location of isolation in Bangladesh, and season of isolation. Genetic profiling was done by enterobacterial repetitive intergenic consensus sequence-PCR, optimized for profiling by using the fully sequenced V. cholerae El Tor N16961 genome. Five significant clonal clusters of haplotypes were found from 57 electrophoretic types. Isolates from different areas or habitats intermingled in two of the five significant clusters. Frequencies of haplotypes differed significantly only between the environmental populations (exact test; P < 0.05). Analysis of molecular variance yielded a population genetic structure reflecting the differentiating effects of geographic area, habitat, and sampling time. Although a parameter confounding the latter differences explained 9% of the total molecular variance in the entire population (P < 0.01), the net effect of habitat and time could not be separated because of the small number of environmental isolates included in the study. Five subpopulations from a single area were determined, and from these we were able to estimate a relative differentiating effect of habitat, which was small compared with the effect of temporal change. In conclusion, the resulting population structure supports the hypothesis that spatial and temporal fluctuations in the composition of toxigenic V. cholerae populations in the aquatic environment can cause shifts in the dynamics of the disease.

Bangladesh↗
PubMed2025

Formation of sensory maps: New tools reveal novel insights into neural development.

The development of functional neural circuits depends on the navigation of neurites (axons and dendrites) through spatially complex and molecularly diverse environments to their appropriate targets. How these processes maneuver through dense surroundings to reach their targets is a long-standing question in neuroscience. Studies of sensory systems have been especially enlightening for identifying cues that underlie connectivity due to their organization as stereotyped neural maps. Recent advances in imaging, connectomics, and genomics have profoundly deepened our understanding of these processes and uncovered new mechanisms regulating circuit development. In this review, we discuss studies of Drosophila sensory systems that provide new insights into axon and dendritic targeting, partner identification and selection, and subcellular refinement. We highlight related or divergent findings in other systems and provide an outlook for future studies.

Animals↗
PubMed2026

Proteomics in environmental pollution research: Advances, challenges, and future directions.

Environmental proteomics has emerged as a powerful approach for elucidating the molecular mechanisms underlying pollutant-induced biological effects. Although this field has developed rapidly, the systematic review of recent proteomics applications in environmental pollution research remains limited. This review explored the emerging roles of toxicoproteomics in biomarker discovery and mechanistic elucidation, as well as ecotoxicoproteomics in ecological risk assessment and bioremediation strategies. Here, we review the field, highlighting recent trends such as the integration of proteomics with genomics, transcriptomics, and metabolomics to provide a comprehensive view of biological responses to environmental stressors. We further discuss the growing application of artificial intelligence in improving proteomics data interpretation and accelerating biomarker discovery. In addition, recent technological advances in environmental proteomics are highlighted, including next-generation tissue microarray proteomics, nanoscale proteomics, single-cell proteomics, and spatial proteomics. Despite its potential, proteomics faces challenges, such as high operational costs, computational complexity in analysis, and technical limitations in low-abundance protein detection. We propose that the convergence of proteomics with artificial intelligence and multi-omics approaches offers promising solutions to these challenges, enhancing the practical application of proteomics in environmental monitoring and risk assessment.

Proteomics↗
PubMed2005

Co-operation between enhancers modulates quantitative expression from the Drosophila Paramyosin/miniparamyosin gene in different muscle types.

The distinct muscles of an organism accumulate different quantities of structural proteins, but always maintaining their stoichiometry. However, the mechanisms that control the levels of these proteins and that co-ordinate muscle gene expression remain to be defined. The paramyosin/miniparamyosin gene encodes two thick filament proteins transcribed from two different promoters. We have analysed the regulatory regions that control expression of this gene and that are situated in the two promoters, the 5' and the internal promoters, both in vivo and in silico. A distal muscle enhancer containing three conserved MEF2 motifs is essential to drive high levels of paramyosin expression in all the major embryonic, larval and adult muscles. This enhancer shares sequence motifs, as well as its structure and organisation, with at least four co-regulated muscle enhancers that direct similar patterns of expression. However, other elements located downstream of the enhancer are also required for correct gene expression. Other muscle genes with different patterns of expression, such as miniparamyosin, are regulated by other basic mechanisms. The expression of miniparamyosin is controlled by two enhancers, AB and TX, but a BF modulator is required to ensure the correct levels of expression in each particular muscle. We propose a mechanism of transcriptional regulation in which similar enhancers are responsible for the spatio-temporal expression of co-regulated genes. However, it is the interaction between enhancers which ensures that the correct amounts of protein are expressed at any particular time in a cell, adapting these levels to their specific needs. These mechanisms may not be exclusive to neural or muscle tissue and might represent a general mechanism for genes that are spatially and temporally co-regulated.

Amino Acid Motifs↗
PubMed2006

The C2H2 zinc finger genes of Strongylocentrotus purpuratus and their expression in embryonic development.

The C2H2 zinc finger is one of the most abundant protein domains and is thought to have been extensively replicated in diverse animal clades. Some well-studied proteins that contain this domain are transcriptional regulators. As part of an attempt to delineate all transcription factors encoded in the Strongylocentrotus purpuratus genome, we identified the C2H2 zinc finger genes indicated in the sequence, and examined their involvement in embryonic development. We found 377 zinc finger genes in the sea urchin genome, about half the number found in mice or humans. Their expression was measured by quantitative PCR. Up to the end of gastrulation less than a third of these genes is expressed, and about 75% of the expressed genes are maternal; both parameters distinguish these from all other classes of regulatory genes as measured in other studies. Spatial expression pattern was determined by whole mount in situ hybridization for 43 genes transcribed at a sufficient level, and localized expression was observed in diverse embryonic tissues. These genes may execute important regulatory functions in development. However, the functional meaning of the majority of this large gene family remains undefined.

Animals↗
PubMed1995

The Drosophila homeotic target gene centrosomin (cnn) encodes a novel centrosomal protein with leucine zippers and maps to a genomic region required for midgut morphogenesis.

The products of the homeotic genes in Drosophila are transcription factors that are necessary to impose regional identity along the anterior-posterior axis of the developing embryo. However, the target genes under homeotic regulation that control this developmental process are largely unknown. We have utilized an immunopurification method to clone target genes of the Antennapedia protein (ANTP). We present here the characterization of centrosomin (cnn), one of the target genes isolated using this approach. The spatial and temporal expression of the cnn gene in the developing visceral mesoderm (VM) of the midgut and the central nervous system (CNS) of wild-type and homeotic mutant embryos is consistent with the idea that cnn is a homeotic target. In the VM, Antp and abdominal-A (abd-A) negatively regulate cnn, while Ultrabithorax (Ubx) shows positive regulation. In the CNS, cnn is regulated positively by Antp and negatively by Ubx and abd-A. Characterization of a cDNA encoding CNN predicts a novel structural protein with three leucine zipper motifs and several coiled-coil domains exhibiting limited homology to the rod portion of myosin. Immunocytochemical results demonstrate that the cnn encoded protein is localized to the centrosome and the accumulation pattern is coupled to the nuclear and centrosome duplication cycles of cleavage. In addition, evidence suggests that the expression of the cnn gene in the VM correlates with the morphogenetic function of Ubx in that tissue, i.e., the formation of the second midgut construction. The centrosomal localization of CNN and the involvement of microtubules in midgut morphogenesis suggest that this protein may participate in mitotic spindle assembly and the mechanics of morphogenesis through an interaction with microtubules, either directly or indirectly.

Amino Acid Sequence↗
PubMed2006

Integrated biclustering of heterogeneous genome-wide datasets for the inference of global regulatory networks.

BACKGROUND: The learning of global genetic regulatory networks from expression data is a severely under-constrained problem that is aided by reducing the dimensionality of the search space by means of clustering genes into putatively co-regulated groups, as opposed to those that are simply co-expressed. Be cause genes may be co-regulated only across a subset of all observed experimental conditions, biclustering (clustering of genes and conditions) is more appropriate than standard clustering. Co-regulated genes are also often functionally (physically, spatially, genetically, and/or evolutionarily) associated, and such a priori known or pre-computed associations can provide support for appropriately grouping genes. One important association is the presence of one or more common cis-regulatory motifs. In organisms where these motifs are not known, their de novo detection, integrated into the clustering algorithm, can help to guide the process towards more biologically parsimonious solutions. RESULTS: We have developed an algorithm, cMonkey, that detects putative co-regulated gene groupings by integrating the biclustering of gene expression data and various functional associations with the de novo detection of sequence motifs. CONCLUSION: We have applied this procedure to the archaeon Halobacterium NRC-1, as part of our efforts to decipher its regulatory network. In addition, we used cMonkey on public data for three organisms in the other two domains of life: Helicobacter pylori, Saccharomyces cerevisiae, and Escherichia coli. The biclusters detected by cMonkey both recapitulated known biology and enabled novel predictions (some for Halobacterium were subsequently confirmed in the laboratory). For example, it identified the bacteriorhodopsin regulon, assigned additional genes to this regulon with apparently unrelated function, and detected its known promoter motif. We have performed a thorough comparison of cMonkey results against other clustering methods, and find that cMonkey biclusters are more parsimonious with all available evidence for co-regulation.

Algorithms↗
PubMed1994

Localized expression of a novel micropia-like element in the blastoderm of Drosophila melanogaster is dependent on the anterior morphogen bicoid.

We have identified a novel transposon-like element of Drosophila melanogaster that is present in approximately 20 copies in the genome. It codes for a polyprotein containing the diagnostic sequence motifs for a nucleic acid binding CCHC protein, a proteinase, a reverse transcriptase and an integrase as typically found in retroviruses. Owing to its early expression in the blastoderm embryo, and its close relationship to micropia, a previously identified Drosophila retrotransposon, we termed the novel element "blastopia". The spatially restricted expression of blastopia transcripts in head anlagen of the blastoderm embryo is under the direct or indirect control of the Drosophila morphogen bicoid, which is normally required to establish the anterior pattern elements in the embryo. Our results suggest that a blastopia element acts as an "enhancer trap", and thereby participates in the control of an as yet unidentified gene normally expressed in the head anlagen of the embryo.

Amino Acid Sequence↗
PubMed2002

Distal regulatory regions restrict the expression of cis-linked genes to the tapetal cells.

The oleosin glycine-rich protein genes Atgrp-6, Atgrp-7, and Atgrp-8 occur in clusters in the Arabidopsis genome and are expressed specifically in the tapetum cells. The cis-regulatory regions involved in the tissue-specific gene expression were investigated by fusing different segments of the gene cluster to the uidA reporter gene. Common distal regulatory regions were identified that coordinate expression of the sequential genes. At least two of these genes were regulated spatially by proximal and distal sequences. The cis-acting elements (122 bp upstream of the transcriptional start point) drive the uidA expression to floral tissues, whereas distal 5' upstream regions restrict the gene activity to tapetal cells.

Arabidopsis↗