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Author(s):  
Chen-Yu Wang ◽  
Chien-Chung Yang ◽  
Li-Der Hsiao ◽  
Chuen-Mao Yang

AbstractExcessive production of reactive oxygen species (ROS) by NADPH oxidase (Nox) resulted in inflammation. The negative regulator of ROS (NRROS) dampens ROS generation during inflammatory responses. 15-Deoxy-∆12,14-prostaglandin J2 (15d-PGJ2) exhibits neuroprotective effects on central nervous system (CNS). However, whether 15d-PGJ2-induced NRROS expression was unknown in rat brain astrocytes (RBA-1). NRROS expression was determined by Western blot, RT/real-time PCR, and promoter activity assays. The signaling components were investigated using pharmacological inhibitors or specific siRNAs. The interaction between transcription factors and the NRROS promoter was investigated by chromatin immunoprecipitation assay. Upregulation of NRROS on the hydrogen peroxide (H2O2)-mediated ROS generation and interleukin 6 (IL-6) secretion was measured. 15d-PGJ2-induced NRROS expression was mediated through PI3K/Akt-dependent activation of Sp1 and FoxO1 and established the essential promoter regions. We demonstrated that 15d-PGJ2 activated PI3K/Akt and following by cooperation between phosphorylated nuclear FoxO1 and Sp1 to initiate the NRROS transcription. In addition, Nrf2 played a key role in NRROS expression induced by 15d-PGJ2 which was mediated through its phosphorylation. Finally, the NRROS stable clones attenuated the H2O2-induced ROS generation and expression of IL-6 through suppressing the Nox-2 activity. These results suggested that 15d-PGJ2-induced NRROS expression is mediated through a PI3K/Akt-dependent FoxO1 and Sp1 phosphorylation, and Nrf2 cascade, which suppresses ROS generation through attenuating the p47phox phosphorylation and gp91phox formation and IL-6 expression in RBA-1 cells. These results confirmed the mechanisms underlying 15d-PGJ2-induced NRROS expression which might be a potential strategy for prevention and management of brain inflammatory and neurodegenerative diseases.


2022 ◽  
Author(s):  
Andrew C. Read ◽  
Trevor Weiss ◽  
Peter A. Crisp ◽  
Zhikai Liang ◽  
Jaclyn Noshay ◽  
...  

The Domains Rearranged Methyltransferases (DRMs) are crucial for RNA-directed DNA methylation (RdDM) in plant species. Setaria viridis is a model monocot species with a relatively compact genome that has limited transposable element content. CRISPR-based genome editing approaches were used to create loss-of-function alleles for the two putative functional DRM genes in S. viridis to probe the role of RdDM. The analysis of drm1ab double mutant plants revealed limited morphological consequences for the loss of RdDM. Whole-genome methylation profiling provided evidence for wide-spread loss of methylation in CHH sequence contexts, particularly in regions with high CHH methylation in wild-type plants. There is also evidence for locus-specific loss of CG and CHG methylation, even in some regions that lack CHH methylation. Transcriptome profiling identified a limited number of genes with altered expression in the drm1ab mutants. The majority of genes with elevated CHH methylation directly surrounding the transcription start site or in nearby promoter regions do not have altered expression in the drm1ab mutant even when this methylation is lost, suggesting limited regulation of gene expression by RdDM. Detailed analysis of the expression of transposable elements identified several transposons that are transcriptionally activated in drm1ab mutants. These transposons likely require active RdDM for maintenance of transcriptional repression.


2022 ◽  
Vol 23 (1) ◽  
pp. 542
Author(s):  
Yan Zhang ◽  
Lanjie Zheng ◽  
Liu Yun ◽  
Li Ji ◽  
Guanhui Li ◽  
...  

Catalases (CATs) are present in almost all living organisms and play important roles in plant development and response to various stresses. However, there is relatively little information on CAT genes in wheat and related Triticeae species. A few studies on CAT family genes in wheat have been reported. In this study, ten CAT proteins (TaCATs) were identified in wheat and classified into three groups based on their phylogenetic features and sequence analysis. The analysis of the structure and motif composition of the TaCAT proteins suggested that a segmental duplication event occurred in the TaCAT gene family. Collinearity relationship analysis among different species showed that there were three orthologous CAT genes in rice and in maize. By analyzing the cis-elements in the promoter regions, we speculated that TaCAT genes expression might be regulated by light, oxygen deficit, methyl jasmonate and abscisic acid, and by transcription factors such as MYB. A Gene Ontology (GO)-based analysis showed that TaCAT proteins may be related to the response to various stresses, are cytoplasm localized, and may function as antioxidant enzymes. RT-qPCR and transcriptome data analyses exhibited distinct expression patterns of TaCAT genes in different tissues and in response to various treatments. In this study, a comprehensive analysis of wheat CAT genes was performed, enriching our knowledge of CAT genes and providing a foundation for further functional analyses of this gene family in wheat.


BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Sergei Reverdatto ◽  
Aparna Prasad ◽  
Jamie L. Belrose ◽  
Xiang Zhang ◽  
Morgan A. Sammons ◽  
...  

Abstract Background Because some of its CNS neurons (e.g., retinal ganglion cells after optic nerve crush (ONC)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (SCI)) lose this capacity as tadpoles metamorphose into frogs, the South African claw-toed frog, Xenopus laevis, offers unique opportunities for exploring differences between regenerative and non-regenerative responses to CNS injury within the same organism. An earlier, three-way RNA-seq study (frog ONC eye, tadpole SCI hindbrain, frog SCI hindbrain) identified genes that regulate chromatin accessibility among those that were differentially expressed in regenerative vs non-regenerative CNS [11]. The current study used whole genome bisulfite sequencing (WGBS) of DNA collected from these same animals at the peak period of axon regeneration to study the extent to which DNA methylation could potentially underlie differences in chromatin accessibility between regenerative and non-regenerative CNS. Results Consistent with the hypothesis that DNA of regenerative CNS is more accessible than that of non-regenerative CNS, DNA from both the regenerative tadpole hindbrain and frog eye was less methylated than that of the non-regenerative frog hindbrain. Also, consistent with observations of CNS injury in mammals, DNA methylation in non-regenerative frog hindbrain decreased after SCI. However, contrary to expectations that the level of DNA methylation would decrease even further with axotomy in regenerative CNS, DNA methylation in these regions instead increased with injury. Injury-induced differences in CpG methylation in regenerative CNS became especially enriched in gene promoter regions, whereas non-CpG methylation differences were more evenly distributed across promoter regions, intergenic, and intragenic regions. In non-regenerative CNS, tissue-related (i.e., regenerative vs. non-regenerative CNS) and injury-induced decreases in promoter region CpG methylation were significantly correlated with increased RNA expression, but the injury-induced, increased CpG methylation seen in regenerative CNS across promoter regions was not, suggesting it was associated with increased rather than decreased chromatin accessibility. This hypothesis received support from observations that in regenerative CNS, many genes exhibiting increased, injury-induced, promoter-associated CpG-methylation also exhibited increased RNA expression and association with histone markers for active promoters and enhancers. DNA immunoprecipitation for 5hmC in optic nerve regeneration found that the promoter-associated increases seen in CpG methylation were distinct from those exhibiting changes in 5hmC. Conclusions Although seemingly paradoxical, the increased injury-associated DNA methylation seen in regenerative CNS has many parallels in stem cells and cancer. Thus, these axotomy-induced changes in DNA methylation in regenerative CNS provide evidence for a novel epigenetic state favoring successful over unsuccessful CNS axon regeneration. The datasets described in this study should help lay the foundations for future studies of the molecular and cellular mechanisms involved. The insights gained should, in turn, help point the way to novel therapeutic approaches for treating CNS injury in mammals.


Agriculture ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 53
Author(s):  
Min Ye ◽  
Bidhan Nayak ◽  
Lei Xiong ◽  
Chao Xie ◽  
Yi Dong ◽  
...  

In many organisms, cytochrome P450 enzymes are the primary detoxifying enzymes. Enhanced P450 activity can be mediated by the emergence of new genes, increased transcription due to mutations in the promoter regions, changes in enzyme structures and functions due to mutations in protein-coding regions, or changes in post-translational modifications; all of these changes are subject to insecticide selection pressure. Multiple signalling pathways and key effector molecules are involved in the regulation of insect P450s. Increased P450 activity is a key mechanism inducing insect resistance. Hence, downregulation of selected P450s is a promising strategy to overcome this resistance. Insect P450 inhibitors that act as insecticide synergists, RNA interference to induce P450 gene silencing, and the use of transgenic insects and crops are examples of strategies utilized to overcome resistance. This article reviews the latest advances in studies related to insect P450s-mediated agrochemical resistance, with focuses on the regulatory mechanisms and associated pest management strategies. Future investigations on the comprehensive regulatory pathways of P450-mediated detoxification, identification of key effectors, and downregulation strategies for P450s will ecologically, economically, and practically improve pest management.


2021 ◽  
Vol 26 (4) ◽  
pp. 175
Author(s):  
Erdianty Setiabudi ◽  
Karlia Meitha ◽  
Fenny Martha Dwivany

Banana is one of the most important commodities for maintaining global food security. Primary metabolic processes during the ripening of banana greatly affect post‐harvest quality, particularly in starch metabolism. The beta‐ amylase (BAM) gene family is known as a group of genes that plays an important role in starch metabolism regulation. In this study, we focused on the characterization and comparative analysis of the BAM gene family in DH Pahang and Pisang Klutuk Wulung (PKW) varieties, these being the AA and BB genomes, respectively. The sequences of BAM gene family were retrieved from the database of Musa acuminata ’DH Pahang’ and Musa balbisiana ’PKW’ genome, then structural and functional characterization was performed, followed by identification of cis‐acting elements in the BAM promoter regions. The results showed that the BAM gene family structure was relatively conserved in both genomes, and a putative BAM11 gene was found, the function of which has not been studied in other plants. Cis‐acting element analysis showed that they were distinct in the copy number and types of elements that were responsive to various phytohormones. This study suggested that the BAM genes involved in ripening are spatiotemporally regulated. However, further functional genomic analysis is required to describe the specific role and regulation of BAM genes during ripening in banana.


2021 ◽  
Author(s):  
Boyi Liao ◽  
Peiran Huang ◽  
Xiangyu Zhang ◽  
Xinyu Wang ◽  
Kaiqian Zhou ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths. Recent studies have demonstrated that deregulation of long noncoding RNAs (lncRNAs), such as abnormal DNA methylation of promoter, is strongly associated with development and progression of diverse malignant tumors. This study investigated the mechanisms and changes in DNA methylation levels of promoter regions of HCC-specific lncRNAs, and alterations of downstream target genes.Methods: LncRNA expression profile data of 8 human HCC tissues and matched normal tissues were obtained. LncRNAs with aberrant methylation were identified through DNA methylation microarray. The biological functions of the lncRNAs were investigated through targeted knockdown of lncRNA-SCARF1 in vitro and in vivo. Furthermore, the downstream targets of lncRNA-SCARF1 were identified through ChIRP-MS.Results: LncRNA-SCARF1 was significantly down-regulated in HCC samples. Hypermethylation in the promoter of lnc-SCARF1 induced its down-regulation in HCC. Over-expression of lnc-SCARF1 inhibited the tumor proliferation and migration ability of HCC cells in vitro and in vivo. Furthermore, CUL9 was found to be a potential downstream target of lncRNA-SCARF1.Conclusion: LncRNA-SCARF1 regulates HCC progression by interacting with CUL9 and may serve as a prognostic biomarker or an effective therapeutic target in HCC.


Animals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 65
Author(s):  
Tahir Usman ◽  
Nawab Ali ◽  
Yachun Wang ◽  
Ying Yu

The present study was designed to evaluate the gene expression and DNA methylation level in the promoter region of the CD4 and the JAK-STAT-pathway-related genes. A total of 24 samples were deployed in the gene expression and 118 samples were used in the DNA methylation study. Student’s t-tests were used to analyze the gene expression and DNA methylation. The evaluation of DNA methylation in promoter regions of JAK2 and STAT5A revealed hypo-methylation levels of CpG sites and higher gene expression in cows diagnosed with mastitis as compared to the healthy control, and vice versa in those with CD4. DNA methylation was negatively correlated with gene expression in JAK2, STAT5A, and CD4 genes. Six, two, and four active transcription factors were identified on the CpG sites in the promoter regions of JAK2, STAT5A, and CD4 genes, respectively. Regarding correlation analysis, the DNA methylation levels of CD4 showed significantly higher positive correlations with somatic cell counts (p < 0.05). Findings of the current study inferred that aberrant DNA methylation in the CpG sites at the 1 kb promoter region in JAK2, STAT5A, and CD4 genes due to mastitis in cows can be used as potential epigenetic markers to estimate bovine mastitis susceptibility in dairy cattle.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Liana Carla Albuquerque Peres Martinho

Obesity is a multifactorial health problem characterized by the excessive accumulation of fat in the body and affects approximately 338 million children and adolescents worldwide. For this reason, this study consisted of a literature review to investigate how the causes and treatments of pediatric obesity are being addressed in light of epigenetic modulation as a factor in metabolic programming. For this, preferentially original articles published in English between the years 2017 to 2021 in the PubMed and Scholar Google databases were searched using the epigenetics descriptors; epigenetic modulation; child obesity; metabolic syndrome, combined with each other. A total of 54,000 articles were returned to searches in PubMed and 16,107,000 in Scholar Google. Fewer than 500 studies jointly addressed epigenetics and aspects of obesity or metabolic syndromes in childhood. Only 14 works matched the search criteria. The most discussed epigenetic mechanism in the literature is DNA methylation, whose rates observed mainly in CpG islands of promoter regions in several genes contribute to the prevention and early diagnosis of obesity and other pediatric comorbidities even before birth, based on the correlation between the epigenetic marks, maternal and paternal health and anthropometric indices. Although experimental studies on infant metabolic programming are scarce, existing knowledge suggests that environmental, nutritional, and energy expenditure changes are capable of modulating the epigenome and reversing marks that induce susceptibility to metabolic comorbidities.


2021 ◽  
Author(s):  
Pauline Brochet ◽  
Barbara Ianni ◽  
Laurie Laugier ◽  
Amanda Farage Frade Frade Barros ◽  
Joao Paulo Silva Nunes ◽  
...  

Chagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic process remains poorly understood, although genetic and epigenetic factors have already been proposed. Based on bulk RNA-seq and EPIC methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. We identified 4 main biological processes associated with the pathology development, including immune response, ion transport, cardiac muscle processes and nervous system. An in-depth study of the transcription factors binding sites in the differentially methylated regions corroborated the importance of these processes. We also conducted a methylation study on blood to identify potential biomarkers for CCC. Our data revealed 198 differentially methylated positions (DMPs) that could serve as biomarkers of the disease, of which 61 are associated with disease severity.


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