Chromatin conformation capture (3C)
and high-throughput 3C (Hi-C)
assays allow the study of three-dimensional (3D) genome structures in cell populations or tissues, based on average proximities of ...folded DNA. However, differences between cells can be observed only by single-cell measurements that avoid ensemble averaging
. To study 3D chromatin organization and dynamics before and after fertilization in flowering plants, we analysed the 3D genomes of rice eggs, sperm cells, unicellular zygotes and shoot mesophyll cells. We show that chromatin architectures of rice eggs and sperm cells are comparable to those of mesophyll cells and are reorganized after fertilization. The rice single-cell 3D genomes display specific features of chromosome compartments and telomere/centromere configuration compared to those in mammalian single cells. Active and silent chromatin domains combine to form multiple foci in the nuclear space. Notably, the 3D genomes of the eggs and unicellular zygotes contain a compact silent centre (CSC) that is absent in sperm cells. CSC appears to be reorganized after fertilization, and may be involved in the regulation of zygotic genome activation (ZGA). Our results reveal specific 3D genome features of plant gametes and the unicellular zygote, and provide a spatial chromatin basis for ZGA and epigenetic regulation in plants.
H3K27me3 is a repressive chromatin mark of genes and is catalyzed by homologs of Enhancer of zeste E(z), a component of Polycomb-repressive complex 2 (PRC2), while DNA methylation that occurs in CG ...and non-CG (CHG and CHH, where H is A, C, or T) contexts is a hallmark of transposon silencing in plants. However, the relationship between H3K27me3 and DNA methylation in gene repression remains unclear. In addition, the mechanism of PRC2 recruitment to specific genes is not known in plants. Here, we show that SDG711, a rice (Oryza sativa) E(z) homolog, is required to maintain H3K27me3 of many developmental genes after shoot meristem to leaf transition and that many H3K27me3-marked developmental genes are also methylated at non-CG sites in the body regions. SDG711-binding and SDG711-mediated ectopic H3K27me3 also target genes methylated at non-CG sites. Conversely, mutation of OsDRM2, a major rice CHH methyltransferase, resulted in loss of SDG711-binding and H3K27me3 from many genes and their de-repression. Furthermore, we show that SDG711 physically interacts with OsDRM2 and a putative CHG methylation-binding protein. These results together suggest that the repression of many developmental genes may involve both DRM2-mediated non-CG methylation and PRC2-mediated H3K27me3 and that the two marks are not generally mutually exclusive but may cooperate in repression of developmentally regulated genes in rice.
Rice inflorescence meristem (IM) activity is essential for panicle development and grain production. How chromatin and epigenetic mechanisms regulate IM activity remains unclear. Genome-wide analysis ...revealed that in addition to genes involved in the vegetative to reproductive transition, many metabolic and protein synthetic genes were activated in IM compared with shoot apical meristem and that a change in the H3K27me3/H3K4me3 ratio was an important factor for the differential expression of many genes. Thousands of genes gained or lost H3K27me3 in IM, and downregulation of the H3K27 methyltransferase gene SET DOMAIN GROUP 711 (SDG711) or mutation of the H3K4 demethylase gene JMJ703 eliminated the increase of H3K27me3 in many genes. SDG711-mediated H3K27me3 repressed several important genes involved in IM activity and many genes that are silent in the IM but activated during floral organogenesis or other developmental stages. SDG711 overexpression augmented IM activity and increased panicle size; suppression of SDG711 by RNA interference had the opposite effect. Double knockdown/knockout of SDG711 and JMJ703 further reduced panicle size. These results suggest that SDG711 and JMJ703 have agonistic functions in reprogramming the H3K27me3/H3K4me3 ratio and modulating gene expression in the IM.
Proteins in the Chromodomain-Helicase/ATPase-DNA-binding domain (CHD) family are divided into three groups. The function of group I CHD proteins in nucleosome positioning is well established, while ...that of group II members (represented by CHD3/Mi2) remains unclear. Using high-throughput approaches, we investigated the function of the group II rice (
) CHD protein CHR729 in nucleosome positioning, gene expression, histone methylation, and binding. Our data revealed that the
mutation led to increased nucleosome occupancy in the rice genome and altered the expression and histone H3K4me3 modification of many, mainly underexpressed, genes. Further analysis showed that the mutation affected both the deposition and depletion of H3K4me3 in distinct chromatin regions, with concomitant changes in H3K27me3 modification. Genetic and genomic analyses revealed that CHR729 and JMJ703, an H3K4 demethylase, had agonistic, antagonistic, and independent functions in modulating H3K4me3 and the expression of subsets of genes. In addition, CHR729 binding was enriched in H3K4me3-marked genic and H3K27me3-marked intergenic regions. The results indicate that CHR729 has distinct functions in regulating H3K4me3 and H3K27me3 modifications and gene expression at different chromatin domains and provide insight into chromatin regulation of bivalent genes marked by both H3K4me3 and H3K27me3.
Histone methylation is an important epigenetic modification in chromatin function, genome activity, and gene regulation. Dimethylated or trimethylated histone H3 lysine 27 (H3K27me2/3) marks silent ...or repressed genes involved in developmental processes and stress responses in plants. However, the role and the mechanism of the dynamic removal of H3K27me2/3 during gene activation remain unclear. Here, we show that the rice (Oryza sativa) Jumonji C (jmjC) protein gene JMJ705 encodes a histone lysine demethylase that specifically reverses H3K27me2/3. The expression of JMJ705 is induced by stress signals and during pathogen infection. Overexpression of the gene reduces the resting level of H3K27me2/3 resulting in preferential activation of H3K27me3-marked biotic stress-responsive genes and enhances rice resistance to the bacterial blight disease pathogen Xanthomonas oryzae pathovar oryzae. Mutation of the gene reduces plant resistance to the pathogen. Further analysis revealed that JMJ705 is involved in methyl jasmonate—induced dynamic removal of H3K27me3 and gene activation. The results suggest that JMJ705 is a biotic stress-responsive H3K27me2/3 demethylase that may remove H3K27me3 from marked defense-related genes and increase their basal and induced expression during pathogen infection.
Background
Systemic inflammatory response syndrome (SIRS) greatly affects postoperative lives of afflicted aged patients. This study aimed to determine whether preoperative high hs-CRP/HDL ratio ...(CHR) was associated with an increased risk of postoperative SIRS in the elderly population.
Methods
This retrospective cohort study included data on patients aged ≥ 65 years who underwent general anesthesia surgery at two clinical centers between January 2015 and September 2020. The primary exposure was preoperative CHR which was divided into two groups (≤ 12.82 and > 12.82) based on its normal range in our hospital, and the primary outcome was the incidence of postoperative SIRS. Targeted maximum likelihood estimation analyses were used to model the exposure–outcome relationship.
Results
The analysis included 5595 elderly patients, of whom 1410 (25.20%) developed SIRS within three postoperative days. Targeted maximum likelihood estimation analysis revealed that elderly patients with CHR > 12.82
vs.
CHR ≤ 12.82 was associated with increased risk of postoperative SIRS (aOR = 1.40, 95% CI 1.33, 1.48,
P
< 0.001). Those results were consistent both in subgroup analyses and sensitivity analyses. Compared with patients with CHR ≤ 12.82, patients with CHR > 12.82 had a higher prevalence of postoperative SIRS (49.06%
vs.
22.70%), postoperative in-hospital mortality (3.40%
vs.
0.65%), a longer hospital stay after surgery 10 (IQR, 6–16)
vs.
8 (IQR, 5–11) days and higher direct medical cost 10070 (IQR, 6878–15577)
vs.
7117 (IQR, 4079–10314) euros, all
P
< 0.001.
Conclusions
In elderly patients, preoperative CHR > 12.82 was significantly associated with a higher risk of postoperative SIRS.
Electroconvulsive therapy (ECT) performed under general anesthesia is an effective treatment for severe depression. Etomidate is an intravenous anesthetic that shows beneficial effects on ECT. ...However, the potential mechanisms have rarely been reported. In this study, male rats were exposed to chronic unpredictable mild stress for 4 weeks, followed by ECT for 10 days, with or without intervention with ferrostatin-1 (2 mg/kg) or all-trans retinoic acid (ATRA, 5 mg/kg). Rats subjected to etomidate (20 mg/kg) or propofol (120 mg/kg) treatment were administered with designated anesthetic before ECT. Compared to depressive rats without ECT, those who received ECT showed increased numbers of hippocampal neurons, increased expression of negative regulators of ferroptosis including glutathione peroxidase 4, ferritin heavy chain 1, and ferroptosis suppressor protein 1, upregulation of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor, and downregulation of acyl-CoA synthetase long-chain family member 4, a positive regulator of ferroptosis in the hippocampus. Additionally, compared with propofol, etomidate used in ECT resulted in higher upregulation of BDNF/Nrf2 and inhibited neuronal ferroptosis in hippocampus. These results showed etomidate may enhance the antidepressant effect of ECT by protecting hippocampal neurons against ferroptosis.
The LAM1 transcription factor regulates expansion of primary leaflets in the compound leaves of tomato, and also affects floral organ development, fruit size, and initiation of secondary leaflets.
...Abstract
Plant-specific WOX family transcription factors play important roles ranging from embryogenesis to lateral organ development. The WOX1 transcription factors, which belong to the modern clade of the WOX family, are known to regulate outgrowth of the leaf blade specifically in the mediolateral axis; however, the role of WOX1 in compound leaf development remains unknown. Phylogenetic analysis of the whole WOX family in tomato (Solanum lycopersicum) indicates that there are 10 members that represent the modern, intermediate, and ancient clades. Using phylogenetic analysis and a reverse genetic approach, in this study we identified SlLAM1 in the modern clade and examined its function and tissue-specific expression pattern. We found that knocking out SlLAM1 via CRISPR/Cas9-mediated genome editing led to narrow leaves and a reduced number of secondary leaflets. Overexpression of tomato SlLAM1 could rescue the defects of the tobacco lam1 mutant. Anatomical and transcriptomic analyses demonstrated that floral organ development, fruit size, secondary leaflet initiation, and leaf complexity were altered due to loss-of-function of SlLAM1. These findings demonstrate that tomato SlLAM1 plays an important role in the regulation of secondary leaflet initiation, in addition to its conserved function in blade expansion.
To investigate the effects of intraoperative application of dexmedetomidine (Dex) on early gastrointestinal motility after laparoscopic resection of colorectal cancer.
In this prospective, randomized ...double-blind investigation, 60 patients who underwent laparoscopic resection of colorectal cancer were randomly allocated to receive Dex (DEX group, n = 30) or saline (CON group, n = 30). In the DEX group, Dex was loaded (1 μg/kg) before anesthesia induction and was infused (0.3 μg/kg/h) during surgery. Time to postoperative first flatus (FFL) and first feces (FFE), and time to regular diet were recorded. Serum diamine oxidase (DAO) activity and intestinal fatty acid-binding protein (I-FABP) were detected.
Both the time to the FFL (44.41 ± 4.51 hours vs 61.03 ± 5.16 hours, P = 0.02) and the time to the FFE (60.67 ± 4.94 hours vs 82.50 ± 6.88 hours, P = 0.014) were significantly shorter in the DEX group than the CON group. Furthermore, the time to regular diet of the DEX group was shorter than that of the CON group (76.15 ± 4.11 hours vs 91.50 ± 5.70 hours, P = 0.037). Both DAO and I-FABP increased significantly from beginning of surgery to postoperative day 1 in the CON group (2.49 ± 0.41 ng/mL vs 4.48 ± 0.94 ng/mL for DAO, P = 0.028, 1.32 ± 0.09 ng/mL vs 2.17 ± 0.12 ng/mL for I-FABP, P = 0.045, respectively), whereas no significant change was observed in the DEX group. Furthermore, patients in the DEX group had stable hemodynamics and shorter hospital stay than those in the CON group.
Dex administration intraoperatively benefits recovery of gastrointestinal motility function after laparoscopic resection of colorectal cancer with stable hemodynamics during surgery though further studies are needed to explore the mechanisms of Dex on gastrointestinal motility.
Optimizing plant architecture is an efficient approach for breeders to increase crop yields, and phytohormones such as gibberellins (GAs) play an important role in controlling growth. Medicago ...truncatula is a model legume species, but the molecular mechanisms underlying its architecture are largely unknown. In this study, we examined a tobacco retrotransposon Tnt1-tagged mutant collection of M. truncatula and identified dwarf and increased branching 1 (dib1), which exhibited extreme dwarfism and increased numbers of lateral branches. By analysis of the flanking sequences of Tnt1 insertions in different alleles of the tagged lines, we were able to clone DIB1. Linkage analysis and reverse screening of the flanking-sequence tags identified Medtr2g102570 as the gene corresponding to the DIB1 locus in the dib1 loss-of-function mutants. Phylogenetic analysis indicated that DIB1 was the ortholog of PsGA3ox1/Le in Pisum sativum. Expression analysis using a GUS-staining reporter line showed that DIB1 was expressed in the root apex, pods, and immature seeds. Endogenous GA4 concentrations were markedly decreased whilst some of representative GA biosynthetic enzymes were up-regulated in the dib1 mutant. In addition, exogenous application of GA3 rescued the dib1 mutant phenotypes. Overall, our results suggest that DIB1 controls plant height and axillary bud outgrowth via an influence on the biosynthesis of bioactive GAs. DIB1 could therefore be a good candidate gene for breeders to optimize plant architecture for crop improvement.
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