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PubMed2000

Molecular cloning, spatial and temporal characterization of spinach SOGA1 cDNA, encoding an alpha subunit of G protein.

Heterotrimeric G proteins are an important component of signal transduction pathway in animals. Although these proteins have been described in plants, their exact function and action mode are not clearly defined. In order to analyze the relationship between these proteins and the transduction of light signals in spinach, we have isolated by 5' and 3' RACE-PCR a 1660bp cDNA clone called SOGA1. This codes for a 383aa protein, which reveals a very strong homology with other plant Galpha subunit sequences. Genomic analysis suggested that SOGA1 belonged to a small multiple gene family. Northern blots and in-situ hybridization analyses showed that SOGA1 transcripts accumulate in all organs tested with a specific high level associated with the apex, roots and hypocotyls. Finally, a time-course analysis performed on the green tissues showed that accumulation of SOGA1 transcripts follows a circadian rhythm. However, in-situ hybridization analysis of the apex suggested the opposite behavior, while no variation was observed in the hypocotyl.

Amino Acid Sequence↗
PubMed1984

Developmental expression of the white locus of Drosophila melanogaster.

We have isolated several cDNA clones of the white locus which are derived from embryonic and pupal transcripts of Drosophila melanogaster. The cDNA sequences map within 7.5 kb (coordinates -3.0 to +4.6) of the genomic DNA and correspond mainly to sequences within the distal region of the gene (coordinates -0.2 to -3.0). A major RNA species of 2.6 kb was detected on Northerns of poly(A) RNA isolated from all developmental stages. The total accumulation of this transcript peaks in the mature third instar larva to a level of 0.003% which is about ten times higher than that observed in embryos. The spatial distribution of white locus transcripts was determined by in situ hybridization to tissue sections. In embryos, hybridization signals are restricted to the cells of the developing Malpighian tubules and the signal strength corresponds with 50 transcripts per cell. Before the termination of the third instar stage, hybridization signals are also detected at a comparable level in the eye antennal disks. At the same stage, a third site of labeling is observed over a small cluster of cells which seems to be associated with the larval photoreceptor organs. Thus, white locus expression is largely restricted to tissues which are known to be involved in the biosynthesis of eye pigments and these different cell types act in a temporally autonomous manner with respect to the induction of the white gene during development.

Journal Article↗
PubMed2005

Chromatin organisation and nuclear architecture in growing mouse oocytes.

Although the female gamete is blocked at the dictyate stage of the first meiotic prophase during the whole folliculogenesis, many important epigenetic changes occur to organise the genome to attend early embryonic development. In this paper, we will describe the results of a number of studies aimed to improve our understanding of the nuclear organization of the mouse oocyte during folliculogenesis. Using silver methods that stain NOR, centromeres and heterochromatin, as well as, the use of specific antibodies for the demonstration of centromeres, we have described the changes to the chromatin organisation and to the spatial localisation of chromocenters and centromeres during oocyte growth; these changes have been correlated to the developmental competence of the resulting antral and metaphase II (MII) oocyte.

Animals↗
PubMed2005

Transcription factor gene expression profiling after acute intermittent nicotine treatment in the rat cerebral cortex.

Several studies in different in vitro and in vivo models have demonstrated neuroprotective effects of nicotinic receptor agonists and indirect trophic actions of nicotine on brain are suggested from observations describing nicotine as a cognitive enhancer by increasing vigilance and improving learning and memory. While an increasing number of studies have given evidence of neuroprotective and neurotrophic effects of nicotine treatment, the molecular mechanism mediating the neurotrophic effects of nicotine are not fully understood. Previously in an analysis of several neurotrophic factors as possible mediators of nicotine-induced neuroprotection and/or neurotrophic effects we could reveal that an acute intermittent nicotine treatment increases fibroblast growth factor-2 mRNA and protein in several brain regions of rat brain. Even if other studies have demonstrated in different paradigms that nicotine administration modulates expression level of a variety of genes, there is still a lack of indication which candidate genes, involved in neuroprotective responses are modulated by nicotine. In the present work we have used a microarray assay to further find and characterize new genes responsive to acute intermittent nicotine treatment and linked to neuroprotection. Therefore, we used Rat Genome U34A Affymetrix GeneChip arrays containing about 8800 probe sets to characterize transcriptional responses in the rat parietal cortex after acute intermittent nicotine treatment. We focused our attention to expression of transcription factors and several of them were up- or down-regulated by nicotine, among these Nr4a1 (Nurr77), Egr-1 and Egr-2. In situ hybridization was used to corroborate the microarray data and to reveal further spatial and temporal patterns of these nicotine induced genes. Taken together the present results identified several novel candidate genes modified by acute intermittent nicotine exposure and as such potentially involved in neuroprotective-neurotrophic actions.

Animals↗
PubMed2026

FZD5 drives macrophage-mediated immunomodulation and predicts prognosis in glioma: evidence from single-cell sequencing.

BACKGROUND: Gliomas are highly malignant brain tumors characterized by an immunosuppressive microenvironment, which limits therapeutic efficacy and contributes to poor clinical outcomes. The WNT/β-catenin signaling pathway is critically involved in tumor progression, and FZD5, a key receptor within this pathway, may participate in immune regulation. However, its specific role and underlying mechanisms in glioma remain unclear. METHODS: RNA-seq and microarray datasets from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA), together with single-cell RNA sequencing (scRNA-seq) datasets from GEO, were comprehensively analyzed. The Seurat package was used to identify macrophage-related clusters and mitophagy-associated pathways. Cox and LASSO regression analyses, along with a prognostic nomogram, were applied to evaluate the prognostic significance of FZD5. Immune infiltration, functional enrichment, and immunotherapy response analyses were conducted, followed by validation using spatial transcriptomics, immunohistochemistry, and in vitro assays. RESULTS: In bulk glioma transcriptomes, FZD5 emerged as an independent predictor of poor prognosis. Crucially, single-cell and spatial analyses revealed that the biologically significant FZD5 signal originated predominantly within tumor-associated macrophages (TAMs), where it colocalized with the M2 marker CD163. Consistently, elevated FZD5 levels correlated with increased myeloid infiltration and an immunosuppressive tumor microenvironment. Functionally, macrophage-expressed FZD5 was associated with mitophagy-related programs and promoted an M2-skewed phenotype, thereby enhancing glioma cell proliferation, migration, and invasion via macrophage-glioma crosstalk. CONCLUSION: FZD5 is a TAM-enriched marker in glioma tissues and a potential regulator of macrophage-associated immunosuppressive programs, supporting its utility as a prognostic biomarker and a candidate target for microenvironment-oriented interventions in glioma.

Humans↗
PubMed2001

Novel roles for mammalian septins: from vesicle trafficking to oncogenesis.

In recent years a convergence of various aspects of cell biology has become apparent, and yet investigators are only beginning to grasp the underlying unifying mechanisms. Among the proteins that participate in diverse aspects of cell biology are the septins. These are a group of novel GTPase proteins that are broadly distributed in many eukaryotes except plants. Although septins were originally identified as a protein family involved in cytokinesis in yeast, recent advances in the field have now ascribed additional functions to these proteins. In particular, the number of known mammalian septin family members has increased dramatically as more data has become available through genome analyses. We suggest a classification for the mammalian septins based on the sequence homologies in their highly divergent N- and C-termini. Recent work suggests novel functions for septins in vesicle trafficking, oncogenesis and compartmentalization of the plasma membrane. Given the ability of the septins to bind GTP and phosphatidylinositol 4,5-bisphosphate in a mutually exclusive manner, these proteins might be crucial elements for the spatial and/or temporal control of diverse cellular functions. As the functions of the septins become unraveled, our understanding of seemingly different cellular processes may move a step further.

Cell Transformation, Neoplastic↗
PubMed2005

Genome-wide analysis of temporally regulated and compartment-specific gene expression in sporulating cells of Bacillus subtilis.

Temporal and compartment-specific control of gene expression during sporulation in Bacillus subtilis is governed by a cascade of four RNA polymerase subunits. sigmaF in the prespore and sigmaE in the mother cell control early stages of development, and are replaced at later stages by sigmaG and sigmaK, respectively. Ultimately, a comprehensive description of the molecular mechanisms underlying spore morphogenesis requires the knowledge of all the intervening genes and their assignment to specific regulons. Here, in an extension of earlier work, DNA macroarrays have been used, and members of the four compartment-specific sporulation regulons have been identified. Genes were identified and grouped based on: i) their temporal expression profile and ii) the use of mutants for each of the four sigma factors and a bofA allele, which allows sigmaK activation in the absence of sigmaG. As a further test, artificial production of active alleles of the sigma factors in non-sporulating cells was employed. A total of 439 genes were found, including previously characterized genes whose transcription is induced during sporulation: 55 in the sigmaF regulon, 154 sigmaE-governed genes, 113 sigmaG-dependent genes, and 132 genes under sigmaK control. The results strengthen the view that the activities of sigmaF, sigmaE, sigmaG and sigmaK are largely compartmentalized, both temporally as well as spatially, and that the major vegetative sigma factor (sigmaA) is active throughout sporulation. The results provide a dynamic picture of the changes in the overall pattern of gene expression in the two compartments of the sporulating cell, and offer insight into the roles of the prespore and the mother cell at different times of spore morphogenesis.

Bacillus subtilis↗
PubMed2004

Ecology of prokaryotic viruses.

The finding that total viral abundance is higher than total prokaryotic abundance and that a significant fraction of the prokaryotic community is infected with phages in aquatic systems has stimulated research on the ecology of prokaryotic viruses and their role in ecosystems. This review treats the ecology of prokaryotic viruses ('phages') in marine, freshwater and soil systems from a 'virus point of view'. The abundance of viruses varies strongly in different environments and is related to bacterial abundance or activity suggesting that the majority of the viruses found in the environment are typically phages. Data on phage diversity are sparse but indicate that phages are extremely diverse in natural systems. Lytic phages are predators of prokaryotes, whereas lysogenic and chronic infections represent a parasitic interaction. Some forms of lysogeny might be described best as mutualism. The little existing ecological data on phage populations indicate a large variety of environmental niches and survival strategies. The host cell is the main resource for phages and the resource quality, i.e., the metabolic state of the host cell, is a critical factor in all steps of the phage life cycle. Virus-induced mortality of prokaryotes varies strongly on a temporal and spatial scale and shows that phages can be important predators of bacterioplankton. This mortality and the release of cell lysis products into the environment can strongly influence microbial food web processes and biogeochemical cycles. Phages can also affect host diversity, e.g., by 'killing the winner' and keeping in check competitively dominant species or populations. Moreover, they mediate gene transfer between prokaryotes, but this remains largely unknown in the environment. Genomics or proteomics are providing us now with powerful tools in phage ecology, but final testing will have to be performed in the environment.

Bacteria↗
PubMed2006

Oleosin gene expression in olive.

To study the spatial and temporal regulation of oleosin gene expression during olive drupe development, a cDNA (OeOLE) was isolated from embryos. The deduced amino acid sequence of 165 amino acid residues exhibits a long central hydrophobic stretch, including the conserved "proline knot" motif. Phylogenetic analysis grouped OeOLE into the class of high (H) molecular weight oleosins. Southern blotting indicated that the gene is represented by 1-2 copies in the olive genome. Transcript analysis revealed that OeOLE is expressed solely in seeds. A similar bell-shaped pattern of expression was observed in both embryos and endosperms. Transcript accumulation starts at late heart embryo stage, reaches maximum levels at mid-torpedo stage and thereafter declines, coinciding the stages of most oil accumulation in those tissues.

Amino Acid Motifs↗
PubMed1993

Fluorescence in situ hybridization.

Spectacular advances in the use of fluorescence in situ hybridization (FISH) for the visualisation of specific DNA sequences in metaphase chromosomes and interphase cells have been made over the last few years making the technique a useful tool in clinical research. One of the biggest impacts has been in the field of detection and diagnosis of human malignancies. Chromosomal translocations, deletions, amplification of specific genes and changes in chromosome number can all be detected in the non-dividing interphase nucleus using probes ranging from whole chromosome 'paints' to individual gene specific probes. Gene mapping has also benefited from advances in FISH technology. Target sequences ranging from one to several hundred kilobases can be visualised on metaphase chromosomes and spatial resolution in interphase cells permits the ordering of two probes over a distance as small as 1000 base pairs. The potential uses of FISH continue to increase with each new technical innovation.

Chromosome Aberrations↗
PubMed2026

Species distribution models predict genome-wide polymorphism and gene flow in an endangered amphibian.

Species distribution models (SDMs) are widely used to predict habitat suitability but their usefulness and accuracy for inferring population health is still debated. Here, we evaluate whether SDM-derived relative habitat suitability (RHS) predicts genome-wide genetic diversity and connectivity-which are key proxies for population health and the functional integrity of landscapes. We addressed this issue in the Yellow-bellied toad (Bombina variegata), an endangered amphibian species with limited dispersal. We combined hierarchical SDMs, integrating both continental-level bioclimatic data and regional-level landscape variables, with genome-wide SNP data from 404 individuals sampled across 92 sites in southeastern France. We then used a multi-scale modelling framework to test the effect of bioclimatic (BRHS) and landscape (LRHS) habitat suitability on observed heterozygosity and pairwise genetic differentiation, accounting for heterogeneous genetic drift using gravity models. Our results show that both BRHS and LRHS are significant predictors of heterozygosity, with their effects expressed at different spatial scales-11 km and 3 km for BRHS and LRHS, respectively. Connectivity patterns also widely varied depending on scale and were best explained by gravity models integrating LRHS, BRHS, and local heterozygosity, underscoring the combined role of landscape resistance and population size in shaping patterns of genetic differentiation. These findings show that SDMs, when carefully calibrated and interpreted, can provide proxies for genetic diversity and landscape resistance in species with limited dispersal.

Journal Article↗
PubMed2003

Protein sequences yield a proteomic code.

Analysis of crystallized protein structures suggests that globular proteins are organized as consecutively connected units of 25-35 residues. These units are closed loops, that is returns of the polypeptide chain trajectory to a close contact with itself. This universal feature of apparently polymer-statistical nature is a basis for a principally novel view on the globular proteins as loop fold structures. The same unit size has been detected in protein sequences translated from complete prokaryotic genomes by positional autocorrelation analysis, which strongly indicates the evolutionary connection of the units. The units are further characterized by prototype sequences matching to their numerous derivatives in the translated genomes. The matches to five strongest prokaryotic prototypes and three prototypes of C. elegans are identified in the sequences of crystallized proteins, and their structures analyzed. Corresponding segments of the polypeptide chains in majority of cases form closed loops, though evolutionary fate of every prototype element is shown to be rather diverse. Then loop ends can be separated by a sequence-wise distant segments and stabilized by the spatial interactions in the context of the overall globular structure. The units belong to a presumably limited spectrum of the sequence prototypes, full repertoire of which would constitute a proteomic code.

Amino Acid Motifs↗
PubMed2002

The dog as a model to study human epididymal function at a molecular level.

Approaches to study human epididymal functions are limited. Therefore, suitable animal models are highly desirable, yet difficult to find among the few species studied on a molecular level to date. This review summarizes our progress in the development of the canine epididymis as an alternative model. Dogs are biomedically a key species because they are subject to many of the same diseases as humans and already serve as a model for a number of human pathologies, including genetic diseases. It is thus consistent that an appraisal of epididymal specific gene expression has been started in the dog, including the molecular cloning and characterization of canine epididymal proteins. These proteins, in addition to a high overall sequence similarity to the human, show a similar tissue distribution, relative abundance and spatial pattern within the epididymis. Moreover, the dog epididymis offers an excellent source for cell culture studies, and immortalization of the canine epididymal duct epithelium has been achieved, encouraging regulatory studies of epididymal gene expression in vitro. Thus, the dog already fulfils many of the criteria of a good model of the human epididymis on a molecular level. Further progress may be expected with the advance of the canine genome project. If there is a genetic basis for male infertility, then the dog provides the advantage of the exploitation of a species that combines a maximum of genetic variation within a species with the capacity to minimize that variation within a defined pedigree.

Animals↗
PubMed2006

Active chromatin hub of the mouse alpha-globin locus forms in a transcription factory of clustered housekeeping genes.

RNA polymerases can be shared by a particular group of genes in a transcription "factory" in nuclei, where transcription may be coordinated in concert with the distribution of coexpressed genes in higher-eukaryote genomes. Moreover, gene expression can be modulated by regulatory elements working over a long distance. Here, we compared the conformation of a 130-kb chromatin region containing the mouse alpha-globin cluster and their flanking housekeeping genes in 14.5-day-postcoitum fetal liver and brain cells. The analysis of chromatin conformation showed that the active alpha1 and alpha2 globin genes and upstream regulatory elements are in close spatial proximity, indicating that looping may function in the transcriptional regulation of the mouse alpha-globin cluster. In fetal liver cells, the active alpha1 and alpha2 genes, but not the inactive zeta gene, colocalize with neighboring housekeeping genes C16orf33, C16orf8, MPG, and C16orf35. This is in sharp contrast with the mouse alpha-globin genes in nonexpressing cells, which are separated from the congregated housekeeping genes. A comparison of RNA polymerase II (Pol II) occupancies showed that active alpha1 and alpha2 gene promoters have a much higher RNA Pol II enrichment in liver than in brain. The RNA Pol II occupancy at the zeta gene promoter, which is specifically repressed during development, is much lower than that at the alpha1 and alpha2 promoters. Thus, the mouse alpha-globin gene cluster may be regulated through moving in or out active globin gene promoters and regulatory elements of a preexisting transcription factory in the nucleus, which is maintained by the flanking clustered housekeeping genes, to activate or inactivate alpha-globin gene expression.

Animals↗
PubMed1986

Identification of primary transcriptional start sites of mouse mitochondrial DNA: accurate in vitro initiation of both heavy- and light-strand transcripts.

The major transcriptional control sequences of vertebrate mitochondrial DNA lie within the displacement loop region. Transcription events initiating in the displacement loop sequence of the mouse genome were identified by 5' end mapping of primary transcripts by S1 nuclease protection and primer extension techniques. Light-strand transcription initiates at a single site, 165 nucleotides upstream of the major heavy-strand origin of replication. Transcription of the heavy strand occurs at two distinct sites, 5 and 13 nucleotides upstream of the gene for phenylalanyl-tRNA, the first heavy-strand-encoded gene. This spatial relationship of the two transcriptional start sites with each other and with the origin of heavy-strand replication and the gene for tRNAPhe is quite similar to that for human mitochondrial DNA. The predominant form of primary heavy-strand transcript in mouse is a short, ca. 75-nucleotide, RNA containing the sequences of tRNAPhe and a few additional nucleotides at the 5' end of tRNAPhe, suggesting that the processing of tRNA involves independent cleavages at the 5' and 3' ends of tRNA sequences.

Animals↗
PubMed1992

The role of Sry in mammalian sex determination.

The testis-determining gene is the Y-linked gene responsible for initiating the developmental pathway leading to testis formation in males. A strategy based on determining the precise chromosomal location of this locus has been used to clone a new gene which has been called SRY in humans (Sry in mice). A variety of studies now show that this is indeed the testis-determining gene. Sry has a spatial and temporal pattern of expression which correlates with the initiation of testis differentiation. The amino acid sequence encoded by the gene suggests that the protein may function as a transcription factor, which fits well with models of sex determination. Some cases of XY sex reversal in humans and mouse have been attributed to mutations in SRY/Sry, indicating that it is normally necessary for testis determination. The finding that a genomic fragment carrying Sry can cause male development in XX mice has proved that Sry is the only gene from the Y chromosome necessary for testis determination.

Animals↗
PubMed1999

Immunological analysis of potato leafroll luteovirus (PLRV) P1 expression identifies a 25 kDa RNA-binding protein derived via P1 processing.

Mono- and polyclonal antibodies directed against different domains of the potato leafroll luteovirus (PLRV) P1 (ORF1) protein were applied to the analysis of P1 expression during PLRV replication in planta. Western analyses detected P1 and a protein of approximately 25 kDa (P1-C25) that accumulated to readily detectable amounts in PLRV-infected plants, but was not detected by in vitro cell-free translation of P1. P1-C25 represents the C-terminus of P1 and is a proteolytic cleavage product produced during P1 processing. On the basis of its molecular weight, the N-terminus of P1-C25 is either identical to or located adjacent to the previously identified PLRV genome-linked protein, VPg. P1-C25 is not associated with virus particles, and subcellular localization experiments detected P1-C25, but not P1, in the membrane and cytoplasmic fractions of PLRV-infected cells. In addition, P1-C25 exhibits nucleic acid-binding properties. On the basis of its biosynthesis, localization and biochemical properties, P1-C25 may facilitate the formation of P1/PLRV RNA complexes in which the spatial proximity allows for covalent bond formation between PLRV RNA and VPg.

Antibodies, Monoclonal↗
PubMed2001

Differential regulation of CENP-A and histone H3 phosphorylation in G2/M.

After DNA replication, cells condense their chromosomes in order to segregate them during mitosis. The condensation process as well as subsequent segregation requires phosphorylation of histone H3 at serine 10. Histone H3 phosphorylation initiates during G2 in pericentric foci prior to H3 phosphorylation in the chromosome arms. Centromere protein A (CENP-A), a histone H3-like protein found uniquely at centromeres, contains a sequence motif similar to that around H3 Ser10, suggesting that CENP-A phosphorylation might be linked to pericentric initiation of histone H3 phosphorylation. To test this hypothesis, we generated peptide antibodies against the putative phosphorylation site of CENP-A. ELISA, western blot and immunocytochemical analyses show that CENP-A is phosphorylated at the shared motif. Simultaneous co-detection demonstrates that phosphorylation of CENP-A and histone H3 are separate events in G2/M. CENP-A phosphorylation occurs after both pericentric initiation and genome-wide stages of histone H3 phosphorylation. Quantitative immunocytochemistry reveals that CENP-A phosphorylation begins in prophase and reaches maximal levels in prometaphase. CENP-A phosphoepitope reactivity is lost during anaphase and becomes undetectable in telophase cells. Duplication of prekinetochores, detected as the doubling of CENP-A foci, occurs prior to complete histone H3 phosphorylation in G2. Mitotic phosphorylation of histone H3-family proteins shows tight spatial and temporal control, occurring in three phases: (1) pericentric H3 phosphorylation, (2) chromosome arm H3 phosphorylation and (3) CENP-A phosphorylation at kinetochores. These observations reveal new cytological landmarks characteristic of G2 progression.

Amino Acid Sequence↗