Gene Regulation In Response Research Articles

Multi-omics Resources for Understanding Gene Regulation in Response to ER Stress in Plants.

Proteotoxic stress of the endoplasmic reticulum (ER) is a potentially lethal condition that ensues when the biosynthetic capacity of the ER is overwhelmed. A sophisticated and largely conserved signaling, known as the unfolded protein response (UPR), is designed to monitor and alleviate ER stress. In plants, the emerging picture of gene regulation by the UPR now appears to be more complex than ever before, requiring multi-omics-enabled network-level approaches to be untangled. In the past decade, with an increasing access and decreasing costs of next-generation sequencing (NGS) and high-throughput protein-DNA interaction (PDI) screening technologies, multitudes of global molecular measurements, known as omics, have been generated and analyzed by the research community to investigate the complex gene regulation of plant UPR. In this chapter, we present a comprehensive catalog of omics resources at different molecular levels (transcriptomes, protein-DNA interactomes, and networks) along with the introduction of key concepts in experimental and computational tools in data generation and analyses. This chapter will serve as a starting point for both experimentalists and bioinformaticians to explore diverse omics datasets for their biological questions in the plant UPR, with likely applications also in other species for conserved mechanisms.

Identification of abiotic stress-responsive genes: a genome-wide analysis of the cytokinin response regulator gene family in rice.

Response regulators (RRs) are implicated in various developmental processes as well as environmental responses by acting as either positive or negative regulators, and are crucial components of cytokinin signaling in plants. We characterized 36 RRs in rice (Oryza sativa L.; Os) using in silico analysis of publicly available data. A comprehensive analysis of OsRR family members covered their physicochemical properties, chromosomal distribution, subcellular localization, phylogeny, gene structure, distribution of conserved motifs and domains, and gene duplication events. Gene Ontology analysis indicated that 22 OsRR genes contribute mainly to the cytokinin response and signal transduction. Predicted cis-elements in RR promoter sequences related to phytohormones and abiotic stresses indicated that RRs are involved in hormonal and environmental responses, supporting previous studies. MicroRNA (miRNA) target analysis showed that 148 miRNAs target 29 OsRR genes. In some cases, multiple RRs are targets of the same miRNA group, and may be controlled by common stimulus responses. Based on the analysis of publicly available gene expression data, OsRR4, OsRR6, OsRR9, OsRR10, OsRR22, OsPRR73 and OsPRR95 were found to be involved in responses to abiotic stresses. Using quantitative reverse transcription polymerase chain reaction we confirmed that six of these RRs, namely OsRR4, OsRR6, OsRR9, OsRR10, OsRR22 and OsPRR73, are involved in the response to salinity, osmotic, alkaline and wounding stresses, and can potentially be used as models to understand molecular mechanisms underlying stress responsiveness.

Genome-wide transcriptomic and biochemical profiling of major depressive disorder: Unravelling association with susceptibility, severity, and antidepressant response

Identifying biomarkers for diagnosing Major Depressive Disorder (MDD), assessing its severity, and guiding treatment is crucial. We conducted whole genome transcriptomic study in North Indian population, and analyzed biochemical parameters. Our longitudinal study investigated gene-expression profiles from 72 drug-free MDD patients and 50 healthy controls(HCs) at baseline and 24 patients after 12-weeks of treatment. Gene expression analyses identified differentially expressed genes(DEGs) associated with MDD susceptibility, symptom severity and treatment response, independently validated by qPCR. Hierarchical clustering revealed distinct expression patterns between MDD and HCs, also between mild and severe cases. Enrichment analyses of significant DEGs revealed inflammatory, apoptosis, and immune-related pathways in MDD susceptibility, severity, and treatment response. Simultaneously, we assessed thirty biochemical parameters in the same cohort, showed significant differences between MDD and HCs in 13 parameters with monocytes, eosinophils, creatinine, SGPT, and total protein remained independent predictors of MDD in a multivariate-regression model. Our study supports the role of altered immune/inflammatory signaling in MDD pathophysiology, offering clinically relevant biochemical parameters and insights into transcriptomic gene regulation in MDD pathogenesis and treatment response.

Transcriptional Regulation and Characterization of Fusarium udum Responsive NBS-LRR Genes in Pigeonpea (Cajanus cajan (L.) Millsp.

Transcriptional Regulation and Characterization of Fusarium udum Responsive NBS-LRR Genes in Pigeonpea (Cajanus cajan (L.) Millsp.

Genome-wide identification of the melon (Cucumis melo L.) response regulator gene family and functional analysis of CmRR6 and CmPRR3 in response to cold stress

The response regulator (RR) gene family play crucial roles in cytokinin signal transduction, plant development, and resistance to abiotic stress. However, there are no reports on the identification and functional characterization of RR genes in melon. In this study, a total of 18 CmRRs were identified and classified into type A, type B, and clock PRRs, based on phylogenetic analysis. Most of the CmRRs displayed tissue-specific expression patterns, and some were induced by cold stress according to two RNA-seq datasets. The expression patterns of CmRR2/6/11/15 and CmPRR2/3 under cold treatment were confirmed by qRT-PCR. Subcellular localization assays indicated that CmRR6 and CmPRR3 were primarily localized in the nucleus and chloroplast. Furthermore, when either CmRR6 or CmPRR3 were silenced using tobacco ringspot virus (TRSV), the cold tolerance of the virus-induced gene silencing (VIGS) melon plants were significantly enhanced, as evidenced by measurements of chlorophyll fluorescence, ion leakage, reactive oxygen, proline, and malondialdehyde levels. Additionally, the expression levels of CmCBF1, CmCBF2, and CmCBF3 were significantly increased in CmRR6-silenced and CmPRR3-silenced plants under cold treatment. Our findings suggest that CmRRs contribute to cold stress responses and provide new insights for further pursuing the molecular mechanisms underlying CmRRs-mediated cold tolerance in melon.

Response of the persistence of heat stress tolerance in winter wheat seedling to heat priming at early growth stages

This study aimed to investigate the impact of heat priming on the heat stress tolerance of winter wheat seedlings. A hydroponic experiment was conducted with four treatments i.e. no priming and no heat stress (CK), no priming with heat stress (NP-HT), priming with no recovery prior to heat stress subjection (PNR-HT), and priming with heat recovery prior to heat stress subjection (PHR-HT). Biomass, chlorophyll index in flag leaves (SPAD), photosynthetic rate (Pn), stomatal conductance (Gs), protein profiling in young leaves using SDS-Page, and the expression level of heat-responsive and antioxidants responsive genes using RT-qPCR were measured to achieve the objective. The results showed that plants with no heat priming and subjected to heat stress had significantly reduced biomass, SPAD, Pn, Gs and protein content. In contrast, plants that received heat priming with or without recovery had better biomass, SPAD, Pn, Gs and protein content, showing the most significant improvement. The analysis of SDS-PAGE showed alterations in the protein patterns, specifically an upregulation of a 60 kDa protein, subsequent to exposure to heat stress. The study also found that heat priming triggered the up regulation of heat and antioxidants responsive genes. In conclusion, the study provides evidence that heat priming is an effective strategy for enhancing the heat stress tolerance of winter wheat and the primed plants that were allowed to recovery before heat stress exposure exhibited better stress tolerance than the primed plants that were immediately exposed to heat stress.

Genome-Wide Mapping of R-Loops in Single Cells Reveals Cell-Type Specific Roles for R-Loops in Hematopoietic Cell Identity

R-loops are three-stranded structures composed of an RNA-DNA hybrid and a single strand of DNA. R-loops play critical roles in gene regulation and pathologic roles in DNA damage response. Current methods to map R-loops require at least 500,000 cells. Consequently, R-loop characterization in primary cells is limited. Furthermore, there are no genomic tools to identify R-loops in single cells. We therefore developed here methods to map genome-wide R-loops at single cell resolution. R-loop mapping in primary stem and mature hematopoietic cell populations, and individual single cells revealed striking cell-type specific R-loops. Current methods to map R-loops utilize immunoprecipitation with a monoclonal antibody (clone “S9.6”) or catalytically inactive, but R-loop binding competent, RNAseH1. Motivated by success mapping chromatin modifications in single cells through fusion of Tn5 transposase to a nanobody as well as insertion of T7 promoters to amplify DNA at sites of transposition, we combined both techniques to identify R-loops in limited cell numbers, down to the single cell level. We used a nanobody-Tn5 fusion to identify S9.6 and developed an orthogonal recombinant fusion protein of enzymatic dead RNAseH1 fused to Tn5 (Figure A). We first applied our nanobody-Tn5 method to identify R-loops bound by S9.6 in mouse lineage-negative c-Kit + bone marrow cells in biological duplicates of increasingly reduced cell numbers (64,000, 32,000, 16,000, and 8,000 cells). This revealed remarkable reproducibility of R-loop detection and characteristics. R-loops identified were sensitive to RNAseH1 and enriched at sites with G/C skew and mitochondrial DNA (a site with abundant physiologic R-loops), suggesting authentic, bona fide R-loops mapped in as few 8,000 cells. We next evaluated R-loops across FACS-isolated hematopoietic stem and mature cells from mouse and human bone marrow. Mapping of R-loops in 10,000 cells in duplicate revealed reproducible R-loops which were characteristic of each cell population. Hierarchical clustering of R-loop profiles delineated mature from stem and progenitor cells and discovered increased abundance of genic R-loops in hematopoietic stem and progenitors relative to mature cells (Figure B). Application of our enzymatic dead RNaseH1/Tn5 fusion protein to CD34 + cells revealed a similar genome-wide distribution of R-loops as with the S9.6/nanobody-Tn5 method. There was high correlation of long- and short-term HSC-specific R-loops with sites characteristic of active transcription (based on H3K4me1/2/3 as well as H3K27Ac). Transcription factor motifs activated in unique hematopoietic cell types were enriched at R-loops within the same cell types. For example, GATA motif usage was enriched at R-loops in CMP, MEP, and erythroid precursors. We also detected massive increases in R-loop abundance at the immunoglobulin heavy chain locus in primary B-cells stimulated to undergo class switch recombination. This provides further proof of our low input method to identify R-loops, as physiologic R-loops are known to occur at this locus to promote class switch recombination. Despite recent advances in single cell genomics there are no single cell maps of R-loops. We therefore profiled R-loops using our nanobody-Tn5, low-input S9.6 CUT&Tag approach in individual human CD34 + and mouse c-Kit + cells. We obtained 1,579 single-cell profiles from human and 1,716 from mouse. Uniform manifold approximation and projection (UMAP) identified 12 clusters in human and 9 mouse hematopoietic clusters. Aggregated single-cell R-loop profiles closely resembled bulk profiles indicating that single-cell data captured features of multi-cell maps. Pseudotime analyses of R-loops inferred LT-HSCs as the shared root of hematopoiesis in both mouse and human and identified seven terminal states without prior knowledge of the number of branches in the hematopoietic development. These data provide the first maps of R-loops in primary normal hematopoietic cells and identify scheduled, physiologic cell-type specific R-loops which have not previously been uncovered. The atlas of R-loops across hematopoiesis generated here will motivate future studies to understand the roles of R-loops in hematopoietic differentiation. Moreover, the methods presented map R-loop abundance at nucleotide resolution in primary and limited cell types which can be used for wide-reaching applications.

Machine Learning Sequence Modeling Identifies Gene Regulatory Responses to Bone Marrow Stromal Interactions in Multiple Myeloma

Introduction Multiple myeloma (MM) is a hematological malignancy of plasma cells which affects different organs including the bone marrow. The interaction between MM and the bone marrow stromal cells (BMSC) has been shown to affect the disease progression and response to treatment (Kumar et al. Multiple myeloma. Nat. Rev. Dis. Primers, 2017). An in vitro system to isolate the signaling mechanisms between BMSC and MM cells has been developed by (Dziadowicz et al., Cancers, 2022), who co-cultured MM cell lines in transwell media (TSW) exposed to BMSC secreted factors and compared their ATAC-seq profiles to MM cell lines (MONO) in isolation without the exposure to BMSC. While some of the gene expression changes induced by the BMSC-MM crosstalk were reported in (Dziadowicz et al., Cancers, 2022), here we model the entire chromatin accessibility profiles with a DNA-sequence based machine learning model to detect the altered Transcription Factor (TF) and enhancer activity responsible for driving the gene expression changes. We used sequence-based machine learning models (Beer et al., 2020, Annu. Rev. Genom. Hum. Genet.) and applied a systematic approach to model the chromatin accessibility changes induced by the interaction of BMSC and MM cells (MM-TSW) vs. MM cell lines cultured in isolation (MM-MONO). Methods We trained gapped-kmer SVM (gkm-SVM) machine learning models on MM1S and RPMI8226 MM cell line ATAC-seq data generated by Dziadowicz et al. as well as 1270 DNase-seq chromatin accessibility profiles of various human primary tissues and cell lines (including MM1S and RPMI8226) from the ENCODE consortium. We trained gkm-SVM on the top 2000 differentially-accessible distal ATAC peaks (>2000bp from transcription start site, e.g. enhancers) to find the differential TF activity between MM-TSW and MM-MONO (Figure 1) and found the TF binding site motifs explaining the gkmSVM output kmer weight distribution (Figure 2). We also identified the set of differentially-expressed TFs and performed gene set enrichment using MSigDB. Results We found that RUNX and Ebox-binding (5‘-CACCTG-3‘) TF family members are the most active TFs in MM1S-MONO and RPMI8226-MONO enhancers (gkmSVM AUROCs~0.92). The contribution of the Ebox TFs to distal chromatin accessibility in the MM cell lines is greater than in any other ENCODE sample (n=1270). Principal Component Analysis (PCA) on distal ATAC peaks compared to promoters showed that the MM transcriptional response to BMSC is more clearly explained by the differences in enhancer activity rather than promoters. This response is driven by dysregulated activity of a set of enhancer regions in MM-TSW compared to MM-MONO (Figure 1) and our machine learning method can identify these regulatory changes (AUROC~0.90). In addition to the altered AP1 and JAK/STAT activity reported by Dziadowicz et al., we discovered that RUNX and Ebox-binding transcriptional activity are downregulated in MM cells following the interaction with BMSC (Figure 2). Although our RNA-seq analysis found differential expression of some Ebox-binding TFs such as TCF3 and ZEB1 and RUNX members, the identification of the exact TF member(s) driving these RUNX and Ebox/E2A downregulation in MM-TSW is still challenging. Furthermore, PCA analysis of the gene expression profiles of MM1S and RPMI8226 cells showed that the targets of Bone Morphogenetic Protein 2 (BMP2) are upregulated in MM-TSW (FDR < 10 -28). Conclusion While some of the gene expression changes induced by the BMSC-MM interaction were reported in (Dziadowicz et al., Cancers, 2022), our modeling of the entire chromatin landscape discovered the previously unreported downregulation of RUNX and Ebox/E2A TFs in MM as the dominant response of MM interacting with BMSCs, accompanied by an upregulation of AP1 and JAK/STAT. RUNX and E2A-binding families of TFs include RUNX1/2/3, ZEB1/2, SNAI1/2 and TCF3, some of which we previously found to be strongly involved in epithelial to mesenchymal transition in gastric cancer and its invasiveness (Razavi-Mohseni et al., submitted, 2023). Bone marrow microenvironment interactions with MM are known to affect the disease progression and treatment, therefore, identifying the set of TFs driving the MM response to stroma may provide better understanding of the disease and better therapeutic opportunities.

Honey bee Apis mellifera L. responses to oxidative stress induced by pharmacological and pesticidal compounds

The western honey bee, Apis mellifera L., is a eusocial insect that plays a significant role in ecosystem balances and the pollination of plants and food crops. Honey bees face multiple biotic and abiotic stressors, such as pathogens, diseases, chemical pesticides, and climate change, which all contribute to honey bee colony loss. This study investigated the impacts of multiple pharmacological and pesticidal molecules on honey bee survival and gene regulation responses. In an 11-day cage experiment, sublethal doses of tunicamycin, thapsigargin, metformin, paraquat, hydrogen peroxide, and imidacloprid were administered to newly emerged sister bees. Daily treatment consumption and mortality were recorded, as well as the transcription expression of 12 major genes (AChE-2, Apisimin, Apidaecin, mrjp1, Sodq, cp450, SelT, SelK, Ire1, Xbp1, Derl-1, and Hsc70), some of which are markers of oxidative and endoplasmic reticulum (ER) stresses in honey bees. At day 9 of the treatments, protein damage was quantified in caged bees. A Kaplan–Meier model indicated significant (p < 0.001) toxicological effects of paraquat, H2O2, and tunicamycin on bee survivorship compared with controls with better survival for other molecules. Post-ingestive aversion responses were recorded only for tunicamycin, hydrogen peroxide, and imidacloprid. Nonetheless, significantly higher protein damage on day 9 was identified only in bees exposed to paraquat and imidacloprid. Some antioxidant genes were significantly regulated vis-à-vis specific treatments. Our results reveal age-related regulation of other major genes with significant inter-gene positive correlations.

Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes

The NFE2L1 transcription factor (aka Nrf1) is a basic leucine zipper protein that performs a critical role in the cellular stress response pathway. Here, we characterized a novel variant of NFE2L1 referred to as NFE2L1-616. The transcript encoding NFE2L1-616 is derived from an intronic promoter, and it has a distinct first exon than other reported full-length NFE2L1 isoforms. The NFE2L1-616 protein constitutively localizes in the nucleus as it lacks the N-terminal amino acid residues that targets other full-length NFE2L1 isoforms to the endoplasmic reticulum. The expression level of NFE2L1-616 is lower than other NFE2L1 isoforms. It is widely expressed across different cell lines and tissues that were examined. NFE2L1-616 showed strong transcriptional activity driving luciferase reporter expression from a promoter containing antioxidant response element. Together, the results suggest that NFE2L1-616 variant can function as a positive regulator in the transcriptional regulation of NFE2L1 responsive genes.

Transcriptomic analysis reveals the beneficial effects of salt priming on enhancing defense responses in upland cotton under successive salt stress.

Priming-mediated stress tolerance in plants stimulates defense mechanisms and enables plants to cope with future stresses. Seed priming has been proven effective for tolerance against abiotic stresses; however, underlying genetic mechanisms are still unknown. We aimed to assess upland cotton genotypes and their transcriptional behaviors under salt priming and successive induced salt stress. We pre-selected 16 genotypes based on previous studies and performed morpho-physiological characterization, from which we selected three genotypes, representing different tolerance levels, for transcriptomic analysis. We subjected these genotypes to four different treatments: salt priming (P0), salt priming with salinity dose at 3-true-leaf stage (PD), salinity dose at 3-true-leaf stage without salt priming (0D), and control (CK). Although the three genotypes displayed distinct expression patterns, we identified common differentially expressed genes (DEGs) under PD enriched in pathways related to transferase activity, terpene synthase activity, lipid biosynthesis, and regulation of acquired resistance, indicating the beneficial role of salt priming in enhancing salt stress resistance. Moreover, the number of unique DEGs associated with G. hirsutum purpurascens was significantly higher compared to other genotypes. Coexpression network analysis identified 16 hub genes involved in cell wall biogenesis, glucan metabolic processes, and ribosomal RNA binding. Functional characterization of XTH6 (XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE) using virus-induced gene silencing revealed that suppressing its expression improves plant growth under salt stress. Overall, findings provide insights into the regulation of candidate genes in response to salt stress and the beneficial effects of salt priming on enhancing defense responses in upland cotton.

DNA Methylation Profiling of Ovarian Tissue of Climbing Perch (Anabas testudienus) in Response to Monocrotophos Exposure.

Epigenetic modifications like DNA methylation can alter an organism's phenotype without changing its DNA sequence. Exposure to environmental toxicants has the potential to change the resilience of aquatic species. However, little information is available on the dynamics of DNA methylation in fish gonadal tissues in response to organophosphates. In the present work, reduced-representation bisulfite sequencing was performed to identify DNA methylation patterns in the ovarian tissues of Anabas testudienus exposed to organophosphates, specifically monocrotophos (MCP). Through sequencing, an average of 41,087 methylated cytosine sites were identified and distributed in different parts of genes, i.e., in transcription start sites (TSS), promoters, exons, etc. A total of 1058 and 1329 differentially methylated regions (DMRs) were detected as hyper-methylated and hypo-methylated in ovarian tissues, respectively. Utilizing whole-genome data of the climbing perch, the DMRs, and their associated overlapping genes revealed a total of 22 genes within exons, 45 genes at transcription start sites (TSS), and 218 genes in intergenic regions. Through gene ontology analysis, a total of 16 GO terms particularly involved in ovarian follicular development, response to oxidative stress, oocyte maturation, and multicellular organismal response to stress associated with reproductive biology were identified. After functional enrichment analysis, relevant DMGs such as steroid hormone biosynthesis (Cyp19a, 11-beta-HSD, 17-beta-HSD), hormone receptors (ar, esrrga), steroid metabolism (StAR), progesterone-mediated oocyte maturation (igf1ar, pgr), associated with ovarian development in climbing perch showed significant differential methylation patterns. The differentially methylated genes (DMGs) were subjected to analysis using real-time PCR, which demonstrated altered gene expression levels. This study revealed a molecular-level alteration in genes associated with ovarian development in response to chemical exposure. This work provides evidence for understanding the relationship between DNA methylation and gene regulation in response to chemicals that affect the reproductive fitness of aquatic animals.

Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation.

Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.

Multilayered regulation of iron homeostasis in Arabidopsis.

Iron (Fe) is an essential micronutrient for plant growth and development due to its role in crucial processes such as photosynthesis and modulation of the redox state as an electron donor. While Fe is one of the five most abundant metals in the Earth's crust, it is poorly accessible to plants in alkaline soils due to the formation of insoluble complexes. To limit Fe deficiency symptoms, plant have developed a highly sophisticated regulation network including Fe sensing, transcriptional regulation of Fe-deficiency responsive genes, and post-translational modifications of Fe transporters. In this mini-review, we detail how plants perceive intracellular Fe status and how they regulate transporters involved in Fe uptake through a complex cascade of transcription factors. We also describe the current knowledge about intracellular trafficking, including secretion to the plasma membrane, endocytosis, recycling, and degradation of the two main Fe transporters, IRON-REGULATED TRANSPORTER 1 (IRT1) and NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1 (NRAMP1). Regulation of these transporters by their non-Fe substrates is discussed in relation to their functional role to avoid accumulation of these toxic metals during Fe limitation.

Genome-Wide Identification of the RR Gene Family and Its Expression Analysis in Response to TDZ Induction in Rhododendron delavayi.

The cytokinin response regulator (RR) gene is essential for cytokinin signal transduction, which plays a crucial role in plant growth and development. Here, we applied bioinformatics to Rhododendron delavayi's genome to identify its RR gene family and systematically analyzed their gene characteristics, phylogenetic evolution, chromosomal localization, collinearity analysis, promoter cis-elements, and expression patterns. Overall, 33 RdRR genes were distinguished and classified into three types. All these genes harbored motif 5 (YEVTTVNSGLEALELLRENKB), the most conserved one, along with the plant-conserved domain (REC domain), and could be mapped to 10 chromosomes with four gene pairs of segmental replication events but no tandem replication events; 13 RdRR genes showed collinearity with Arabidopsis thaliana genes. Promoter analysis revealed multiple hormone-related cis-elements in the RR genes. After a TDZ (thidiazuron) treatment, 13 genes had higher expression levels than the control, whose magnitude of change depended on the developmental stage of leaves' adventitious buds. The expression levels of RdRR14, RdRR17, RdRR20, and RdRR24 agreed with the average number of adventitious buds post-TDZ treatment. We speculate that these four genes could figure prominently in bud regeneration from R. delavayi leaves in vitro. This study provides detailed knowledge of RdRRs for research on cytokinin signaling and RdRR functioning in R. delavayi.

Regulation of core interferon response genes in Atlantic salmon in response to Poly I:C

Regulation of core interferon response genes in Atlantic salmon in response to Poly I:C

A translational regulator MHZ9 modulates ethylene signaling in rice

Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through analysis of an ethylene-response mutant mhz9, we identified a glycine-tyrosine-phenylalanine (GYF) domain protein MHZ9, which positively regulates ethylene signaling at translational level in rice. MHZ9 is localized in RNA processing bodies. The C-terminal domain of MHZ9 interacts with OsEIN2, a central regulator of rice ethylene signaling, and the N-terminal domain directly binds to the OsEBF1/2 mRNAs for translational inhibition, allowing accumulation of transcription factor OsEIL1 to activate the downstream signaling. RNA-IP seq and CLIP-seq analyses reveal that MHZ9 associates with hundreds of RNAs. Ribo-seq analysis indicates that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene. Our study identifies a translational regulator MHZ9, which mediates translational regulation of genes in response to ethylene, facilitating stress adaptation and trait improvement in rice.

SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3.

The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its noncatalytic FLOS domain-mediated recruitment of cyclin K and regulation of DNA damage response genes. In this study, we identify a functional nuclear localization signal in and interaction partners of the FLOS domain. Our screen for FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3. Inhibition of both cyclin K and BuGZ/BUB3-binding motifs in SETD1A shows synergistic antileukemic effects. BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions adjacent to SETD1A target genes. The GLEBS motif and intrinsically disordered region of BuGZ are required forboth SETD1A-binding and leukemia cell proliferation. Cell-cycle-specific SETD1A restoration assays indicate that SETD1A expression at the G1/S phase of the cell cycle promotes both the expression of DNA damage response genes and cell cycle progression in leukemia cells.

Salt stress responses and alleviation strategies in legumes: a review of the current knowledge.

Salinity is one of the most significant environmental factors limiting legumes development and productivity. Salt stress disturbs all developmental stages of legumes and affects their hormonal regulation, photosynthesis and biological nitrogen fixation, causing nutritional imbalance, plant growth inhibition and yield losses. At the molecular level, salt stress exposure involves large number of factors that are implicated in stress perception, transduction, and regulation of salt responsive genes' expression through the intervention of transcription factors. Along with the complex gene network, epigenetic regulation mediated by non-coding RNAs, and DNA methylation events are also involved in legumes' response to salinity. Different alleviation strategies can increase salt tolerance in legume plants. The most promising ones are Plant Growth Promoting Rhizobia, Arbuscular Mycorrhizal Fungi, seed and plant's priming. Genetic manipulation offers an effective approach for improving salt tolerance. In this review, we present a detailed overview of the adverse effect of salt stress on legumes and their molecular responses. We also provide an overview of various ameliorative strategies that have been implemented to mitigate/overcome the harmful effects of salt stress on legumes.

Effect of germ-free status on transcriptional profiles in the nucleus accumbens and transcriptomic response to chronic morphine

Opioid use disorder is a public health crisis that causes tremendous suffering for patients as well as substantial social and economic costs for society. There are currently available treatments for patients with opioid use disorder, but they remain intolerable or ineffective for many. Thus the need to develop new avenues for therapeutics development in this space is great. Substantial work in models of substance use disorders, including opioid use disorder, demonstrates that prolonged exposure to drugs of abuse leads to marked transcriptional and epigenetic dysregulation in limbic substructures. It is widely believed that these changes in gene regulation in response to drugs are a key driving factor in the perpetuation of drug taking and seeking behaviors. Thus, development of interventions that could shape transcriptional regulation in response to drugs of abuse would be of high value. Over the past decade there has been a surge in research demonstrating that the resident bacteria of the gastrointestinal tract, collectively the gut microbiome, can have tremendous influence on neurobiological and behavioral plasticity. Previous work from our group and others has demonstrated that alterations in the gut microbiome can alter behavioral responses to opioids in multiple paradigms. Additionally, we have previously reported that depletion of the gut microbiome with antibiotics markedly shifts the transcriptome of the nucleus accumbens following prolonged morphine exposure. In this manuscript we present a comprehensive analysis of the effects of the gut microbiome on transcriptional regulation of the nucleus accumbens following morphine by utilizing germ-free, antibiotic treated, and control mice. This allows for detailed understanding of the role of the microbiome in regulating baseline transcriptomic control, as well as response to morphine. We find that germ-free status leads to a marked gene dysregulation in a manner distinct to adult mice treated with antibiotics, and that altered gene pathways are highly related to cellular metabolic processes. These data provide additional insight into the role of the gut microbiome in modulating brain function and lay a foundation for further study in this area.