ABSTRACT
Population expansion is a global issue, especially for food production. Meanwhile, global climate change is damaging our soils, making it difficult for crops to thrive and lowering both production and quality. Poor nutrition and salinity stress affect plant growth and development. Although the impact of individual plant stresses has been studied for decades, the real stress scenario is more complex due to the exposure to multiple stresses at the same time. Here we investigate using existing evidence and a meta-analysis approach to determine molecular linkages between two contemporaneous abiotic stimuli, phosphate (Pi) deficiency and salinity, on a single plant cell model, the root hairs (RHs), which is the first plant cell exposed to them. Understanding how these two stresses work molecularly in RHs may help us build super-adaptable crops and sustainable agriculture in the face of global climate change.
ABSTRACT
Sulfur (S) is an essential macronutrient for plants and its availability in soils is an important determinant for growth and development. Current regulatory policies aimed at reducing industrial S emissions together with changes in agronomical practices have led to a decline in S contents in soils worldwide. Deficiency of sulfate-the primary form of S accessible to plants in soil-has adverse effects on both crop yield and nutritional quality. Hence, recent research has increasingly focused on unraveling the molecular mechanisms through which plants detect and adapt to a limiting supply of sulfate. A significant part of these studies involves the use of omics technologies and has generated comprehensive catalogs of sulfate deficiency-responsive genes and processes, principally in Arabidopsis together with a few studies centering on crop species such as wheat, rice, or members of the Brassica genus. Although we know that sulfate deficiency elicits an important reprogramming of the transcriptome, the transcriptional regulators orchestrating this response are not yet well understood. In this review, we summarize our current knowledge of gene expression responses to sulfate deficiency and recent efforts towards the identification of the transcription factors that are involved in controlling these responses. We further compare the transcriptional response and putative regulators between Arabidopsis and two important crop species, rice and tomato, to gain insights into common mechanisms of the response to sulfate deficiency.
Subject(s)
Gene Expression Regulation, Plant , Gene Regulatory Networks , Sulfates , Sulfates/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/growth & development , Arabidopsis/physiology , Oryza/genetics , Oryza/metabolism , Oryza/growth & developmentABSTRACT
Iron is the most abundant micronutrient in plant mitochondria, and it has a crucial role in biochemical reactions involving electron transfer. It has been described in Oryza sativa that Mitochondrial Iron Transporter (MIT) is an essential gene and that knockdown mutant rice plants have a decreased amount of iron in their mitochondria, strongly suggesting that OsMIT is involved in mitochondrial iron uptake. In Arabidopsis thaliana, two genes encode MIT homologues. In this study, we analyzed different AtMIT1 and AtMIT2 mutant alleles, and no phenotypic defects were observed in individual mutant plants grown in normal conditions, confirming that neither AtMIT1 nor AtMIT2 are individually essential. When we generated crosses between the Atmit1 and Atmit2 alleles, we were able to isolate homozygous double mutant plants. Interestingly, homozygous double mutant plants were obtained only when mutant alleles of Atmit2 with the T-DNA insertion in the intron region were used for crossings, and in these cases, a correctly spliced AtMIT2 mRNA was generated, although at a low level. Atmit1 Atmit2 double homozygous mutant plants, knockout for AtMIT1 and knockdown for AtMIT2, were grown and characterized in iron-sufficient conditions. Pleiotropic developmental defects were observed, including abnormal seeds, an increased number of cotyledons, a slow growth rate, pinoid stems, defects in flower structures, and reduced seed set. A RNA-Seq study was performed, and we could identify more than 760 genes differentially expressed in Atmit1 Atmit2. Our results show that Atmit1 Atmit2 double homozygous mutant plants misregulate genes involved in iron transport, coumarin metabolism, hormone metabolism, root development, and stress-related response. The phenotypes observed, such as pinoid stems and fused cotyledons, in Atmit1 Atmit2 double homozygous mutant plants may suggest defects in auxin homeostasis. Unexpectedly, we observed a possible phenomenon of T-DNA suppression in the next generation of Atmit1 Atmit2 double homozygous mutant plants, correlating with increased splicing of the AtMIT2 intron containing the T-DNA and the suppression of the phenotypes observed in the first generation of the double mutant plants. In these plants with a suppressed phenotype, no differences were observed in the oxygen consumption rate of isolated mitochondria; however, the molecular analysis of gene expression markers, AOX1a, UPOX, and MSM1, for mitochondrial and oxidative stress showed that these plants express a degree of mitochondrial perturbation. Finally, we could establish by a targeted proteomic analysis that a protein level of 30% of MIT2, in the absence of MIT1, is enough for normal plant growth under iron-sufficient conditions.
ABSTRACT
LSUs (RESPONSE TO LOW SULFUR) are plant-specific proteins of unknown function that were initially identified during transcriptomic studies of the sulfur deficiency response in Arabidopsis. Recent functional studies have shown that LSUs are important hubs of protein interaction networks with potential roles in plant stress responses. In particular, LSU proteins have been reported to interact with members of the brassinosteroid, jasmonate signaling, and ethylene biosynthetic pathways, suggesting that LSUs may be involved in response to plant stress through modulation of phytohormones. Furthermore, in silico analysis of the promoter regions of LSU genes in Arabidopsis has revealed the presence of cis-regulatory elements that are potentially responsive to phytohormones such as ABA, auxin, and jasmonic acid, suggesting crosstalk between LSU proteins and phytohormones. In this review, we summarize current knowledge about the LSU gene family in plants and its potential role in phytohormone responses.
Subject(s)
Arabidopsis , Plant Growth Regulators , Plant Growth Regulators/genetics , Plant Growth Regulators/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Indoleacetic Acids/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Sulfur/metabolism , Gene Expression Regulation, Plant , Stress, Physiological/geneticsABSTRACT
Piscirickettsia salmonis is the most important health problem facing Chilean Aquaculture. Previous reports suggest that P. salmonis can survive in salmonid macrophages by interfering with the host immune response. However, the relevant aspects of the molecular pathogenesis of P. salmonis have been poorly characterized. In this work, we evaluated the transcriptomic changes in macrophage-like cell line SHK-1 infected with P. salmonis at 24- and 48-hours post-infection (hpi) and generated network models of the macrophage response to the infection using co-expression analysis and regulatory transcription factor-target gene information. Transcriptomic analysis showed that 635 genes were differentially expressed after 24- and/or 48-hpi. The pattern of expression of these genes was analyzed by weighted co-expression network analysis (WGCNA), which classified genes into 4 modules of expression, comprising early responses to the bacterium. Induced genes included genes involved in metabolism and cell differentiation, intracellular transportation, and cytoskeleton reorganization, while repressed genes included genes involved in extracellular matrix organization and RNA metabolism. To understand how these expression changes are orchestrated and to pinpoint relevant transcription factors (TFs) controlling the response, we established a curated database of TF-target gene regulatory interactions in Salmo salar, SalSaDB. Using this resource, together with co-expression module data, we generated infection context-specific networks that were analyzed to determine highly connected TF nodes. We found that the most connected TF of the 24- and 48-hpi response networks is KLF17, an ortholog of the KLF4 TF involved in the polarization of macrophages to an M2-phenotype in mammals. Interestingly, while KLF17 is induced by P. salmonis infection, other TFs, such as NOTCH3 and NFATC1, whose orthologs in mammals are related to M1-like macrophages, are repressed. In sum, our results suggest the induction of early regulatory events associated with an M2-like phenotype of macrophages that drives effectors related to the lysosome, RNA metabolism, cytoskeleton organization, and extracellular matrix remodeling. Moreover, the M1-like response seems delayed in generating an effective response, suggesting a polarization towards M2-like macrophages that allows the survival of P. salmonis. This work also contributes to SalSaDB, a curated database of TF-target gene interactions that is freely available for the Atlantic salmon community.
Subject(s)
Salmo salar , Animals , Salmo salar/genetics , Gene Expression Profiling , Macrophages/metabolism , Transcription Factors/metabolism , RNA/metabolism , MammalsABSTRACT
RNA interference is an ancient mechanism with many regulatory roles in eukaryotic genomes, with small RNAs acting as their functional element. While there is a wide array of classes of small-RNA-producing loci, those resulting from stem-loop structures (hairpins) have received profuse attention. Such is the case of microRNAs (miRNAs), which have distinct roles in plants and animals. Fungi also produce small RNAs, and several publications have identified miRNAs and miRNA-like (mi/milRNA) hairpin RNAs in diverse fungal species using deep sequencing technologies. Despite this relevant source of information, relatively little is known about mi/milRNA features in fungi, mostly due to a lack of established criteria for their annotation. To systematically assess mi/milRNA characteristics and annotation confidence, we searched for publications describing mi/milRNA loci and re-assessed the annotations for 41 fungal species. We extracted and normalized the annotation data for 1727 reported mi/milRNA loci and determined their abundance profiles, concluding that less than half of the reported loci passed basic standards used for hairpin RNA discovery. We found that fungal mi/milRNA are generally more similar in size to animal miRNAs and were frequently associated with protein-coding genes. The compiled genomic analyses identified 25 mi/milRNA loci conserved in multiple species. Our pipeline allowed us to build a general hierarchy of locus quality, identifying more than 150 loci with high-quality annotations. We provide a centralized annotation of identified mi/milRNA hairpin RNAs in fungi which will serve as a resource for future research and advance in understanding the characteristics and functions of mi/milRNAs in fungal organisms.
Subject(s)
MicroRNAs , RNA, Fungal , Animals , RNA, Fungal/genetics , RNA, Fungal/chemistry , Gene Expression Regulation, Fungal , MicroRNAs/genetics , RNA Interference , Fungi/geneticsABSTRACT
MicroRNAs (miRNAs) are small noncoding RNAs that are key players in the regulation of gene expression. In the past decade, with the increasing accessibility of high-throughput sequencing technologies, different methods have been developed to identify miRNAs, most of which rely on preexisting reference genomes. However, when a reference genome is absent or is not of high quality, such identification becomes more difficult. In this context, we developed BrumiR, an algorithm that is able to discover miRNAs directly and exclusively from small RNA (sRNA) sequencing (sRNA-seq) data. We benchmarked BrumiR with datasets encompassing animal and plant species using real and simulated sRNA-seq experiments. The results demonstrate that BrumiR reaches the highest recall for miRNA discovery, while at the same time being much faster and more efficient than the state-of-the-art tools evaluated. The latter allows BrumiR to analyze a large number of sRNA-seq experiments, from plants or animal species. Moreover, BrumiR detects additional information regarding other expressed sequences (sRNAs, isomiRs, etc.), thus maximizing the biological insight gained from sRNA-seq experiments. Additionally, when a reference genome is available, BrumiR provides a new mapping tool (BrumiR2reference) that performs an a posteriori exhaustive search to identify the precursor sequences. Finally, we also provide a machine learning classifier based on a random forest model that evaluates the sequence-derived features to further refine the prediction obtained from the BrumiR-core. The code of BrumiR and all the algorithms that compose the BrumiR toolkit are freely available at https://github.com/camoragaq/BrumiR.
Subject(s)
MicroRNAs , RNA, Small Untranslated , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Software , Sequence Analysis, RNA/methods , High-Throughput Nucleotide Sequencing/methods , RNA, Small Untranslated/geneticsABSTRACT
LSU proteins belong to a plant-specific gene family initially characterized by their strong induction in response to sulfate (S) deficiency. In the last few years, LSUs have arisen as relevant hubs in protein-protein interaction networks, in which they play relevant roles in the response to abiotic and biotic stresses. Most of our knowledge on LSU genomic organization, expression and function comes from studies in Arabidopsis and tobacco, while little is known about the LSU gene repertoire and evolution of this family in land plants. In this work, a total of 270 LSU family members were identified using 134 land plant species with whole-genome sequences available. Phylogenetic analysis revealed that LSU genes belong to a Spermatophyta-specific gene family, and their homologs are distributed in three major groups, two for dicotyledons and one group for monocotyledons. Protein sequence analyses showed four new motifs that further support the subgroup classification by phylogenetic analyses. Moreover, we analyzed the expression of LSU genes in one representative species of each phylogenetic group (wheat, tomato and Arabidopsis) and found a conserved response to S deficiency, suggesting that these genes might play a key role in S stress responses. In summary, our results indicate that LSU genes belong to the Spermatophyta-specific gene family and their response to S deficiency is conserved in angiosperms.
ABSTRACT
Iron is an essential micronutrient for humans and other organisms. Its deficiency is one of the leading causes of anemia worldwide. The world health organization has proposed that an alternative to increasing iron content in food is through crop biofortification. One of the most consumed part of crops is the seed, however, little is known about how iron accumulation in seed occurs and how it is regulated. B3 transcription factors play a critical role in the accumulation of storage compounds such as proteins and lipids. Their role in seed maturation has been well characterized. However, their relevance in accumulation and distribution of micronutrients like iron remains unknown. In Arabidopsis thaliana and other plant models, three master regulators belonging to the B3 transcription factors family have been identified: FUSCA3 (FUS3), LEAFY COTYLEDON2 (LEC2), and ABSCISIC ACID INSENSITIVE 3 (ABI3). In this work, we studied how seed iron homeostasis is affected in B3 transcription factors mutants using histological and molecular approaches. We determined that iron distribution is modified in abi3, lec2, and fus3 embryo mutants. For abi3-6 and fus3-3 mutant embryos, iron was less accumulated in vacuoles of cells surrounding provasculature compared with wild type embryos. lec2-1 embryos showed no difference in the pattern of iron distribution in hypocotyl, but a dramatic decrease of iron was observed in cotyledons. Interestingly, for the three mutant genotypes, total iron content in dry mutant seeds showed no difference compared to wild type. At the molecular level, we showed that genes encoding the iron storage ferritins proteins are misregulated in mutant seeds. Altogether our results support a role of the B3 transcription factors ABI3, LEC2, and FUS3 in maintaining iron homeostasis in Arabidopsis embryos.
ABSTRACT
Nitrate is a nutrient and a potent signal that impacts global gene expression in plants. However, the regulatory factors controlling temporal and cell type-specific nitrate responses remain largely unknown. We assayed nitrate-responsive transcriptome changes in five major root cell types of the Arabidopsis thaliana root as a function of time. We found that gene-expression response to nitrate is dynamic and highly localized and predicted cell type-specific transcription factor (TF)-target interactions. Among cell types, the endodermis stands out as having the largest and most connected nitrate-regulatory gene network. ABF2 and ABF3 are major hubs for transcriptional responses in the endodermis cell layer. We experimentally validated TF-target interactions for ABF2 and ABF3 by chromatin immunoprecipitation followed by sequencing and a cell-based system to detect TF regulation genome-wide. Validated targets of ABF2 and ABF3 account for more than 50% of the nitrate-responsive transcriptome in the endodermis. Moreover, ABF2 and ABF3 are involved in nitrate-induced lateral root growth. Our approach offers an unprecedented spatiotemporal resolution of the root response to nitrate and identifies important components of cell-specific gene regulatory networks.
Subject(s)
Arabidopsis Proteins/genetics , Basic-Leucine Zipper Transcription Factors/genetics , DNA-Binding Proteins/genetics , Gene Expression Regulation, Plant , Nitrates/metabolism , Plant Physiological Phenomena , Transcription Factors/genetics , Arabidopsis/physiology , Arabidopsis Proteins/metabolism , Basic-Leucine Zipper Transcription Factors/metabolism , Computational Biology/methods , DNA-Binding Proteins/metabolism , Gene Expression Profiling , Gene Ontology , Gene Regulatory Networks , Models, Biological , Organ Specificity/genetics , Plant Roots/physiology , Transcription Factors/metabolism , TranscriptomeABSTRACT
Botrytis cinerea and Trichoderma atroviride are two relevant fungi in agricultural systems. To gain insights into these organisms' transcriptional gene regulatory networks (GRNs), we generated a manually curated transcription factor (TF) dataset for each of them, followed by a GRN inference utilizing available sequence motifs describing DNA-binding specificity and global gene expression data. As a proof of concept of the usefulness of this resource to pinpoint key transcriptional regulators, we employed publicly available transcriptomics data and a newly generated dual RNA-seq dataset to build context-specific Botrytis and Trichoderma GRNs under two different biological paradigms: exposure to continuous light and Botrytis-Trichoderma confrontation assays. Network analysis of fungal responses to constant light revealed striking differences in the transcriptional landscape of both fungi. On the other hand, we found that the confrontation of both microorganisms elicited a distinct set of differentially expressed genes with changes in T. atroviride exceeding those in B. cinerea. Using our regulatory network data, we were able to determine, in both fungi, central TFs involved in this interaction response, including TFs controlling a large set of extracellular peptidases in the biocontrol agent T. atroviride. In summary, our work provides a comprehensive catalog of transcription factors and regulatory interactions for both organisms. This catalog can now serve as a basis for generating novel hypotheses on transcriptional regulatory circuits in different experimental contexts.
ABSTRACT
During mating, males provide not only the spermatozoa to fertilize the oocyte but also other stimuli that are essential for initiating and maintaining the reproductive programme in females. In the mammalian oviduct, mating regulates sperm storage, egg transport, fertilization, early embryonic development, and oestradiol metabolism. However, the main molecules underlying these processes are poorly understood. Using microarray analyses, we identified 58 genes that were either induced or repressed by mating in the endosalpinx at 3 h post-stimulus. RT-qPCR confirmed that mating downregulated the expression of the Oas1h and Prim1 genes and upregulated the expression of the Ceacam1, Chad, Chst10, Slc5a3 and Slc26a4 genes. The functional category 'cell-to-cell signalling and interaction' was over-represented in this gene list. Network modelling identified TNF and all-trans retinoic acid (RA) as upstream regulators of the mating-induced transcriptional response, which was confirmed by intraoviductal injection of TNF or RA in unmated rats. It partially mimicked the transcriptional effect of mating in the rat endosalpinx. Furthermore, mating decreased RA levels in oviductal fluid, and RA-receptor-gamma (RARG) exhibited a nuclear location in oviductal epithelium in both unmated and mated rats, indicating RA-RARG transcriptional activity. In conclusion, the early transcriptional response regulated by mating in the rat endosalpinx is mediated by TNF and RA. These signalling molecules regulate a cohort of genes involved in 'cell-to-cell signalling and interactions' and merit further studies to understand the specific processes activated in the endosalpinx to sustain the events that occur in the mammalian oviduct early after mating.
Subject(s)
Oviducts/metabolism , Sexual Behavior, Animal/physiology , Transcriptome , Tretinoin/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Female , Gene Expression Regulation , Male , Mucous Membrane/metabolism , Rats, Sprague-Dawley , Receptors, Retinoic Acid/metabolism , Retinoic Acid Receptor gammaABSTRACT
Plants possess a robust metabolic network for sensing and controlling reactive oxygen species (ROS) levels upon stress conditions. Evidence shown here supports a role for TGA class II transcription factors as critical regulators of genes controlling ROS levels in the tolerance response to UV-B stress in Arabidopsis. First, tga256 mutant plants showed reduced capacity to scavenge H2O2 and restrict oxidative damage in response to UV-B, and also to methylviologen-induced photooxidative stress. The TGA2 transgene (tga256/TGA2 plants) complemented these phenotypes. Second, RNAseq followed by clustering and Gene Ontology term analyses indicate that TGA2/5/6 positively control the UV-B-induced expression of a group of genes with oxidoreductase, glutathione transferase, and glucosyltransferase activities, such as members of the glutathione S-transferase Tau subfamily (GSTU), which encodes peroxide-scavenging enzymes. Accordingly, increased glutathione peroxidase activity triggered by UV-B was impaired in tga256 mutants. Third, the function of TGA2/5/6 as transcriptional activators of GSTU genes in the UV-B response was confirmed for GSTU7, GSTU8, and GSTU25, using quantitative reverse transcription-PCR and ChIP analyses. Fourth, expression of the GSTU7 transgene complemented the UV-B-susceptible phenotype of tga256 mutant plants. Together, this evidence indicates that TGA2/5/6 factors are key regulators of the antioxidant/detoxifying response to an abiotic stress such as UV-B light overexposure.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Oxidative Stress , Transcription Factors , Ultraviolet Rays , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/radiation effects , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Hydrogen Peroxide/metabolism , Reactive Oxygen Species/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: Sulfur is a major component of biological molecules and thus an essential element for plants. Deficiency of sulfate, the main source of sulfur in soils, negatively influences plant growth and crop yield. The effect of sulfate deficiency on plants has been well characterized at the physiological, transcriptomic and metabolomic levels in Arabidopsis thaliana and a limited number of crop plants. However, we still lack a thorough understanding of the molecular mechanisms and regulatory networks underlying sulfate deficiency in most plants. In this work we analyzed the impact of sulfate starvation on the transcriptome of tomato plants to identify regulatory networks and key transcriptional regulators at a temporal and organ scale. RESULTS: Sulfate starvation reduces the growth of roots and leaves which is accompanied by major changes in the organ transcriptome, with the response being temporally earlier in roots than leaves. Comparative analysis showed that a major part of the Arabidopsis and tomato transcriptomic response to sulfate starvation is conserved between these plants and allowed for the identification of processes specifically regulated in tomato at the transcript level, including the control of internal phosphate levels. Integrative gene network analysis uncovered key transcription factors controlling the temporal expression of genes involved in sulfate assimilation, as well as cell cycle, cell division and photosynthesis during sulfate starvation in tomato roots and leaves. Interestingly, one of these transcription factors presents a high identity with SULFUR LIMITATION1, a central component of the sulfate starvation response in Arabidopsis. CONCLUSIONS: Together, our results provide the first comprehensive catalog of sulfate-responsive genes in tomato, as well as novel regulatory targets for future functional analyses in tomato and other crops.
Subject(s)
Gene Expression Regulation, Plant , Solanum lycopersicum/growth & development , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Sulfates/metabolism , Sulfur/deficiency , Sulfur/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Plant Leaves/growth & development , Plant Leaves/metabolism , Plant Roots/growth & development , Plant Roots/metabolismABSTRACT
Nitrogen (N) is an essential macronutrient for plants and a major limiting factor for plant growth and crop production. Nitrate is the main source of N available to plants in agricultural soils and in many natural environments. Sustaining agricultural productivity is of paramount importance in the current scenario of increasing world population, diversification of crop uses, and climate change. Plant productivity for major crops around the world, however, is still supported by excess application of N-rich fertilizers with detrimental economic and environmental impacts. Thus, understanding how plants regulate nitrate uptake and metabolism is key for developing new crops with enhanced N use efficiency and to cope with future world food demands. The study of plant responses to nitrate has gained considerable interest over the last 30 years. This review provides an overview of key findings in nitrate research, spanning biochemistry, molecular genetics, genomics, and systems biology. We discuss how we have reached our current view of nitrate transport, local and systemic nitrate sensing/signaling, and the regulatory networks underlying nitrate-controlled outputs in plants. We hope this summary will serve not only as a timeline and information repository but also as a baseline to define outstanding questions for future research.
Subject(s)
Nitrates/metabolism , Nitrogen/metabolism , Plant Proteins/metabolism , Plants/metabolism , Anion Transport Proteins/genetics , Anion Transport Proteins/metabolism , Biological Transport , Crops, Agricultural/metabolism , Gene Expression Regulation, Plant , Nitrate Transporters , Plant Proteins/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Whole human genome sequencing initiatives help us understand population history and the basis of genetic diseases. Current data mostly focuses on Old World populations, and the information of the genomic structure of Native Americans, especially those from the Southern Cone is scant. Here we present annotation and variant discovery from high-quality complete genome sequences of a cohort of 11 Mapuche-Huilliche individuals (HUI) from Southern Chile. We found approximately 3.1 × 106 single nucleotide variants (SNVs) per individual and identified 403,383 (6.9%) of novel SNVs events. Analyses of large-scale genomic events detected 680 copy number variants (CNVs) and 4,514 structural variants (SVs), including 398 and 1,910 novel events, respectively. Global ancestry composition of HUI genomes revealed that the cohort represents a sample from a marginally admixed population from the Southern Cone, whose main genetic component derives from Native American ancestors. Additionally, we found that HUI genomes contain variants in genes associated with 5 of the 6 leading causes of noncommunicable diseases in Chile, which may have an impact on the risk of prevalent diseases in Chilean and Amerindian populations. Our data represents a useful resource that can contribute to population-based studies and for the design of early diagnostics or prevention tools for Native and admixed Latin American populations.
Subject(s)
Ethnicity/genetics , Genetic Markers , Genetics, Population , Genome, Human , Genomics/methods , Polymorphism, Single Nucleotide , Whole Genome Sequencing/methods , Adult , Aged , Aged, 80 and over , Chile , Cohort Studies , DNA Copy Number Variations , Female , Haplotypes , Humans , Male , Middle Aged , Young AdultABSTRACT
Studies conducted in rodents subjected to chronic stress and some observations in humans after psychosocial stress, have allowed to establish a link between stress and the susceptibility to many complex diseases, including mood disorders. The studies in rodents have revealed that chronic exposure to stress negatively affects synaptic plasticity by triggering changes in the production of trophic factors, subunit levels of glutamate ionotropic receptors, neuron morphology, and neurogenesis in the adult hippocampus. These modifications may account for the impairment in learning and memory processes observed in chronically stressed animals. It is plausible then, that stress modifies the interplay between signal transduction cascades and gene expression regulation in the hippocampus, therefore leading to altered neuroplasticity and functioning of neural circuits. Considering that miRNAs play an important role in post-transcriptional-regulation of gene expression and participate in several hippocampus-dependent functions; we evaluated the consequences of chronic stress on the expression of miRNAs in dorsal (anterior) portion of the hippocampus, which participates in memory formation in rodents. Here, we show that male rats exposed to daily restraint stress (2.5 h/day) during 7 and 14 days display a differential profile of miRNA levels in dorsal hippocampus and remarkably, we found that some of these miRNAs belong to the miR-379-410 cluster. We confirmed a rise in miR-92a and miR-485 levels after 14 days of stress by qPCR, an effect that was not mimicked by chronic administration of corticosterone (14 days). Our in silico study identified the top-10 biological functions influenced by miR-92a, nine of which were shared with miR-485: Nervous system development and function, Tissue development, Behavior, Embryonic development, Organ development, Organismal development, Organismal survival, Tissue morphology, and Organ morphology. Furthermore, our in silico study provided a landscape of potential miRNA-92a and miR-485 targets, along with relevant canonical pathways related to axonal guidance signaling and cAMP signaling, which may influence the functioning of several neuroplastic substrates in dorsal hippocampus. Additionally, the combined effect of miR-92a and miR-485 on transcription factors, along with histone-modifying enzymes, may have a functional relevance by producing changes in gene regulatory networks that modify the neuroplastic capacity of the adult dorsal hippocampus under stress.
ABSTRACT
The reproductive success of plants largely depends on the correct programming of developmental phase transitions, particularly the shift from vegetative to reproductive growth. The timing of this transition is finely regulated by the integration of an array of environmental and endogenous factors. Nitrogen is the mineral macronutrient that plants require in the largest amount, and as such its availability greatly impacts on many aspects of plant growth and development, including flowering time. We found that nitrate signaling interacts with the age-related and gibberellic acid pathways to control flowering time in Arabidopsis thaliana. We revealed that repressors of flowering time belonging to the AP2-type transcription factor family including SCHLAFMUTZE (SMZ) and SCHNARCHZAPFEN (SNZ) are important regulators of flowering time in response to nitrate. Our results support a model whereby nitrate activates SMZ and SNZ via the gibberellin pathway to repress flowering time in Arabidopsis thaliana.
Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/physiology , Flowers/growth & development , Gene Expression Regulation, Plant , Gibberellins/metabolism , Nitrates/metabolism , Transcription Factors/genetics , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Flowers/genetics , Signal Transduction , Transcription Factors/metabolismABSTRACT
Summary: GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. Availability and Implementation: GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . Contact: genius.psbl@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online.
Subject(s)
Gene Regulatory Networks , Machine Learning , Software , Arabidopsis/geneticsABSTRACT
Development of crops with improved nitrogen use efficiency (NUE) is essential for sustainable agriculture. However, achieving this goal has proven difficult since NUE is a complex trait encompassing physiological and developmental processes. We thought to tackle this problem by taking a systems biology approach to identify candidate target genes. First, we used a supervised machine-learning algorithm to predict a NUE gene network in Arabidopsis (Arabidopsis thaliana). Second, we identified BT2, a member of the Bric-a-Brac/Tramtrack/Broad gene family, as the most central and connected gene in the NUE network. Third, we experimentally tested BT2 for a role in NUE. We found NUE decreased in plants overexpressing BT2 gene compared to wild-type plants under limiting nitrate conditions. In addition, NUE increased compared to wild-type plants under low nitrate conditions in double mutant plants in bt2 and its closely related homolog bt1, indicating a functional redundancy of BT1 and BT2 for NUE. Expression of the nitrate transporter genes NRT2.1 and NRT2.4 increased in the bt1/bt2 double mutant compared to wild-type plants, with a concomitant 65% increase in nitrate uptake under low nitrate conditions. Similar to Arabidopsis, we found that mutation of the BT1/BT2 ortholog gene in rice (Oryza sativa) OsBT increased NUE by 20% compared to wild-type rice plants under low nitrogen conditions. These results indicate BT gene family members act as conserved negative regulators of nitrate uptake genes and NUE in plants and highlight them as prime targets for future strategies to improve NUE in crops.