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31.
Richard G. A. B. Sewalt Johan van der Vlag Marco J. Gunster Karien M. Hamer Jan L. den Blaauwen David P. E. Satijn Thijs Hendrix Roel van Driel Arie P. Otte 《Molecular and cellular biology》1998,18(6):3586-3595
In Drosophila melanogaster, the Polycomb-group (PcG) and trithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxG gene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog of eed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs (esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.In Drosophila melanogaster, the genes of the Polycomb group (PcG) and trithorax group (trxG) are part of a cellular memory system, which is responsible for the stable inheritance of gene activity. The PcG and trxG genes have been identified in Drosophila as repressors (PcG) (18, 22, 27, 28, 38) and activators (trxG) (20, 21), respectively, of homeotic gene activity. PcG and trxG genes were originally found in Drosophila, but mammalian homologs have also been identified and appear to function like their Drosophila homologs (reviewed in reference 37). It has been proposed that PcG proteins repress gene expression through the formation of multimeric protein complexes. We have recently shown that the human PcG proteins HPH1 and HPH2 coimmunoprecipitate, cofractionate, and colocalize in nuclear domains with the human PcG proteins BMI1 (2, 12, 33) and HPC2, a recently identified, novel human Polycomb protein (33, 34). Furthermore, we have found that the human RING1 protein coimmunoprecipitates and colocalizes with HPC2 and other PcG proteins, indicating that RING1 is associated with, or is part of, the mammalian PcG complex (33, 35). These results indicate that mammalian PcG proteins form a multimeric protein complex. This observation is in agreement with observations that different PcG proteins, including Pc, bind in overlapping patterns on polytene chromosomes in Drosophila salivary gland cells (4, 10, 29).Interestingly, also the trithorax gene product trx colocalizes with Drosophila PcG proteins at many sites on polytene chromosomes (6, 24). Even more strikingly, binding of the trx protein has been mapped to small DNA fragments that also contain binding sites for PcG proteins, the Polycomb response elements (5, 6). This finding is further substantiated by the observation that GAGA factor, the gene product of the trxG gene trithorax-like (Trl) (13), colocalizes with Pc protein within the close vicinity of a Polycomb response element (41). Furthermore, the PcG gene Enhancer of zeste [E(z)] contains a domain with sequence homology with the activator protein trx (17). This observation is in agreement with genetic data which indicate that E(z) can be considered both a PcG gene and a trxG gene (26). Double mutations of E(z) and trxG genes result in homeotic phenotypes which are similar to the homeotic phenotypes which are also observed in double mutants of trxG genes (26). Finally, polytene chromosome binding of the trx protein is strongly reduced in homozygous E(z) mutants (4), and vice versa, polytene chromosome binding of the E(z) protein is reduced in trx mutants (24). These data suggest functional interactions between activators (trxG proteins) and repressors (PcG proteins) that are important for their mode of action.To start to investigate these puzzling features of the E(z) gene product, we used the two-hybrid system (8, 9) in order to identify proteins that interact with a mammalian homolog of E(z), the Enx1/EZH2 protein (15, 16). Here, we report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog of eed, a murine PcG gene (7, 36) which has extensive homology with the Drosophila PcG gene extra sex combs (esc) (14, 32, 39). Whereas Enx1/EZH2 and EED coimmunoprecipitate, they neither coimmunoprecipitate nor colocalize with other human PcG proteins, such as HPC2 and BMI1. Our findings indicate that both Enx1/EZH2 and EED form a class of mammalian PcG proteins that is distinct from previously described human PcG proteins. 相似文献
32.
Interdisciplinary research is increasingly recognized as the solution to today’s challenging scientific and societal problems, but the relationship between interdisciplinary research and scientific impact is still unclear. This paper studies the association between the degree of interdisciplinarity and the number of citations at the paper level. Different from previous studies compositing various aspects of interdisciplinarity into a single indicator, we use factor analysis to uncover distinct dimensions of interdisciplinarity corresponding to variety, balance, and disparity. We estimate Poisson models with journal fixed effects and robust standard errors to analyze the divergent relationships between these three factors and citations. We find that long-term (13-year) citations (1) increase at an increasing rate with variety, (2) decrease with balance, and (3) increase at a decreasing rate with disparity. Furthermore, interdisciplinarity also affects the process of citation accumulation: (1) although variety and disparity have positive effects on long-term citations, they have negative effects on short-term (3-year) citations, and (2) although balance has a negative effect on long-term citations, its negative effect is insignificant in the short run. These findings have important implications for interdisciplinary research and science policy. 相似文献
33.
In all but the most sterile environments bacteria will reside in fluid being transported through conduits and some of these will attach and grow as biofilms on the conduit walls. The concentration and diversity of bacteria in the fluid at the point of delivery will be a mix of those when it entered the conduit and those that have become entrained into the flow due to seeding from biofilms. Examples include fluids through conduits such as drinking water pipe networks, endotracheal tubes, catheters and ventilation systems. Here we present two probabilistic models to describe changes in the composition of bulk fluid microbial communities as they are transported through a conduit whilst exposed to biofilm communities. The first (discrete) model simulates absolute numbers of individual cells, whereas the other (continuous) model simulates the relative abundance of taxa in the bulk fluid. The discrete model is founded on a birth-death process whereby the community changes one individual at a time and the numbers of cells in the system can vary. The continuous model is a stochastic differential equation derived from the discrete model and can also accommodate changes in the carrying capacity of the bulk fluid. These models provide a novel Lagrangian framework to investigate and predict the dynamics of migrating microbial communities. In this paper we compare the two models, discuss their merits, possible applications and present simulation results in the context of drinking water distribution systems. Our results provide novel insight into the effects of stochastic dynamics on the composition of non-stationary microbial communities that are exposed to biofilms and provides a new avenue for modelling microbial dynamics in systems where fluids are being transported. 相似文献
34.
35.
Bert Hidding Bart A. Nolet Thijs de Boer Peter P. de Vries Marcel Klaassen 《Oecologia》2010,162(1):199-208
At least two distinct trade-offs are thought to facilitate higher diversity in productive plant communities under herbivory. Higher investment in defence and enhanced colonization potential may both correlate with decreased competitive ability in plants. Herbivory may thus promote coexistence of plant species exhibiting divergent life history strategies. How different seasonally tied herbivore assemblages simultaneously affect plant community composition and diversity is, however, largely unknown. Two contrasting types of herbivory can be distinguished in the aquatic vegetation of the shallow lake Lauwersmeer. In summer, predominantly above-ground tissues are eaten, whereas in winter, waterfowl forage on below-ground plant propagules. In a 4-year exclosure study we experimentally separated above-ground herbivory by waterfowl and large fish in summer from below-ground herbivory by Bewick’s swans in winter. We measured the individual and combined effects of both herbivory periods on the composition of the three-species aquatic plant community. Herbivory effect sizes varied considerably from year to year. In 2 years herbivore exclusion in summer reinforced dominance of Potamogeton pectinatus with a concomitant decrease in Potamogeton pusillus, whereas no strong, unequivocal effect was observed in the other 2 years. Winter exclusion, on the other hand, had a negative effect on Zannichellia palustris, but the effect size differed considerably between years. We suggest that the colonization ability of Z. palustris may have enabled this species to be more abundant after reduction of P. pectinatus tuber densities by swans. Evenness decreased due to herbivore exclusion in summer. We conclude that seasonally tied above- and below-ground herbivory may each stimulate different components of a macrophyte community as they each favoured a different subordinate plant species. 相似文献
36.
Casper C. Hoogenraad Ioana Popa Kensuke Futai Emma Sanchez-Martinez Phebe S. Wulf Thijs van Vlijmen Bjorn R. Dortland Viola Oorschot Roland Govers Maria Monti Albert J. R. Heck Morgan Sheng Judith Klumperman Holger Rehmann Dick Jaarsma Lukas C. Kapitein Peter van der Sluijs 《PLoS biology》2010,8(1)
The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites. We show that GRASP-1 is necessary for AMPA receptor recycling, maintenance of spine morphology, and synaptic plasticity. At the molecular level, GRASP-1 segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes and coordinates the coupling to Rab11-labelled recycling endosomes by interacting with the endosomal SNARE syntaxin 13. We propose that GRASP-1 connects early and late recycling endosomal compartments by forming a molecular bridge between Rab-specific membrane domains and the endosomal SNARE machinery. The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking. 相似文献
37.
The significance of photosynthetic and transpiration rates for the perception by plants of light gradients in leaf canopies has been investigated with regard to nitrogen allocation and re-allocation. A gradient of photon flux density (PFD) over a plant's foliage was simulated by shading one leaf of a pair of primary leaves of bean ( Phaseolus vulgaris L. cv. Rentegever). Photosynthetic rate was manipulated independently of PFD and, to some extent, also of transpiration, by subjecting the leaf to different CO2 concentrations. Transpiration rate was changed independently of PFD and photosynthetic rate by subjecting the leaf to different vapour pressure differences (VPD). A reduced partial pressure of CO2 reduced specific leaf mass (SLM) as did a decreased PFD, but did not change leaf N per unit area (NLA ) and light saturated rate of photosynthesis (Amax ). A reduced VPD caused several effects consistent with the effect of PFD. It decreased NLA and Amax and increased the chlorophyll to N ratio in old and young leaves. Furthermore, it decreased the chlorophyll a to b ratio and inhibited leaf growth in young leaves. The transpiration stream is partitioned among the leaves of a plant according to their transpiration rates. The results suggest that relative rates of import of xylem sap into leaves of a plant play an important role in the perception of partial shading of a plant, a situation normally found in dense vegetations. The possible role of cytokinin influx into leaves as controlled by transpiration rate, is discussed. 相似文献
38.
Ethylene insensitivity results in down-regulation of rubisco expression and photosynthetic capacity in tobacco 总被引:2,自引:0,他引:2
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Little is known about the effect of hormones on the photosynthetic process. Therefore, we studied Rubisco content and expression along with gas exchange parameters in transgenic tobacco (Nicotiana tabacum) plants that are not able to sense ethylene. We also tested for a possible interaction between ethylene insensitivity, abscisic acid (ABA), and sugar feedback on photosynthesis. We measured Rubisco content in seedlings grown in agar with or without added sugar and fluridone, and Rubisco expression in hydroponically grown vegetative plants grown at low and high CO(2). Furthermore, we analyzed gas exchange and the photosynthetic machinery of transformants and wild-type plants grown under standard conditions. In the presence of exogenous glucose (Glc), agar-grown seedlings of the ethylene-insensitive genotype had lower amounts of Rubisco per unit leaf area than the wild type. No differences in Rubisco content were found between ethylene-insensitive and wild-type seedlings treated with fluridone, suggesting that inhibition of ABA production nullified the effect of Glc application. When larger, vegetative plants were grown at different atmospheric CO(2) concentrations, a negative correlation was found between Glc concentration in the leaves and Rubisco gene expression, with stronger repression by high Glc concentrations in ethylene-insensitive plants. Ethylene insensitivity resulted in plants with comparable fractions of nitrogen invested in light harvesting, but lower amounts in electron transport and Rubisco. Consequently, photosynthetic capacity of the insensitive genotype was clearly lower compared with the wild type. We conclude that the inability to perceive ethylene results in increased sensitivity to Glc, which may be mediated by a higher ABA concentration. This increased sensitivity to endogenous Glc has negative consequences for Rubisco content and photosynthetic capacity of these plants. 相似文献
39.
Seasonal encoding by the circadian pacemaker of the SCN 总被引:1,自引:0,他引:1
VanderLeest HT Houben T Michel S Deboer T Albus H Vansteensel MJ Block GD Meijer JH 《Current biology : CB》2007,17(5):468-473
The circadian pacemaker of the suprachiasmatic nucleus (SCN) functions as a seasonal clock through its ability to encode day length [1-6]. To investigate the mechanism by which SCN neurons code for day length, we housed mice under long (LD 16:8) and short (LD 8:16) photoperiods. Electrophysiological recordings of multiunit activity (MUA) in the SCN of freely moving mice revealed broad activity profiles in long days and compressed activity profiles in short days. The patterns remained consistent after release of the mice in constant darkness. Recordings of MUA in acutely prepared hypothalamic slices showed similar differences between the SCN electrical activity patterns in vitro in long and short days. In vitro recordings of neuronal subpopulations revealed that the width of the MUA activity profiles was determined by the distribution of phases of contributing units within the SCN. The subpopulation patterns displayed a significantly broader distribution in long days than in short days. Long-term recordings of single-unit activity revealed short durations of elevated activity in both short and long days (3.48 and 3.85 hr, respectively). The data indicate that coding for day length involves plasticity within SCN neuronal networks in which the phase distribution of oscillating neurons carries information on the photoperiod's duration. 相似文献
40.
NR4A nuclear orphan receptors: protective in vascular disease? 总被引:1,自引:0,他引:1
PURPOSE OF REVIEW: The nuclear orphan receptors Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3) are known to be involved in T-cell apoptosis, brain development, and the hypothalamic-pituitary-adrenal axis. Here, we review our current understanding of the NR4A nuclear receptors in processes that are relevant to vascular disease. RECENT FINDINGS: NR4A nuclear receptors have recently been described to play a role in metabolism by regulating gluconeogenesis, lipolysis, energy expenditure, and adipogenesis. The function of NR4A nuclear receptors has also extensively been investigated in cells crucial in vascular lesion formation, such as macrophages, endothelial cells and smooth muscle cells. SUMMARY: The involvement of NR4A nuclear receptors in both metabolism and in processes in the vessel wall supports a substantial role for NR4A nuclear receptors in the development of vascular disease. 相似文献