scholarly journals Analysis on the Meiosis-Related Gene (Dmc1, Ph1) Expression in Autotriploid Carassius auratus

2019 ◽  
Vol 21 (6) ◽  
pp. 753-761
Author(s):  
Qinbo Qin ◽  
Yuwei Zhou ◽  
Chongqing Wang ◽  
Minghe Zhang ◽  
Huan Qin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Carassius Auratus ◽  
Water System ◽  
High Expression ◽  
Expression Level ◽  
Abnormal Behavior ◽  
Related Gene ◽  
Triploid Fish ◽  
Normal Meiosis

Abstract Triploid is usually considered to be unable to perform normal meiosis due to the abnormal behavior of the three sets of chromosomes. But autotriploid Carassius auratus in the Dongting water system (3n = 150, abbreviated as 3nCC) can perform normal meiosis. In artificial autotriploid Carassius auratus (3n = 150, abbreviated as 3nRR), female individuals undergo normal meiosis and produce mature gametes, while male individuals cannot. To better understand the effects of triploidization on meiosis in fish, we study the structure, methylation level, and expression level of meiosis-related genes (Dmc1, Ph1) in diploid Carassius auratus (2n = 100, abbreviated as 2nCC), Carassius auratus red var.(2n = 100, abbreviated as RCC), 3nCC and 3nRR. The results show that, compared with their diploid ancestors (2nCC and RCC), Dmc1 and Ph1 genes are hypomethylated in all 3nCC and female 3nRR, while are hypermethylated in male 3nRR. Correspondingly, Dmc1 and Ph1 genes are highly expressed in all 3nCC and female 3nRR, while are lowly expressed in male 3nRR. These results indicate that high expression of meiosis-related genes can contribute to restoration of bivalent pairing during meiosis in autotriploid Carassius auratus. This study provides new insights into the effect of DNA methylation on the fertility in triploid fish.

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

scholarly journals The Prognostic Value of RASGEF1A RNA Expression and DNA Methylation in Cytogenetically Normal Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Xue He ◽  
Weilong Zhang ◽  
Wei Fu ◽  
Xiaoni Liu ◽  
Ping Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
High Expression ◽  
Expression Level ◽  
Rna Expression ◽  
Relationship Of ◽  
The Relationship ◽  
Acute Myeloid ◽  
High Expression Level

Abstract Background Acute myeloid leukemia (AML) is a significantly heterogeneous malignancy of the blood. Cytogenetic abnormalities are crucial for the prognosis of AML. However, since more than half of patients with AML are cytogenetically normal AML (CN-AML), new markers are badly required for predicting prognosis. In recent years, gene abnormalities are considered to be strong prognostic factors of CN-AML, already having clinical significance for treatment. In addition, the relationship of methylation in some genes and AML prognosis predicting has been discovered. RASGEF1A is a guanine nucleotide exchange factors of Ras, and has been reported to relate to malignancy. However, there is no research about the relationship of RASGEF1A gene and CN-AML. Methods By integrating the Cancer Genome Atlas (TCGA) database 75 patients with CN-AML and 240 Gene Expression Omnibus (GEO) database CN-AML samples, we examined the association between RASGEF1A ’s RNA expression level and DNA methylation of and AML patients’ prognosis. Then, we investigated the RASGEF1A RNA expression and DNA methylation’s prognostic value in 77 patients with AML after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) as well as 101 AML patients after chemotherapy respectively. We investigated the association between sensitivity to Crenolanib and expression level of RASGED1A in patients by integrating 191 CN-AML patients from BeatAML dadataset. Finally, we integrated the expression and methylation of RASGEF1A to predict the CN-AML patients’ prognosis. Results We found that RASGEF1A gene high expression group predicted poorer event-free survival (EFS) (P < 0.0001) as well as overall survival (OS) (P < 0.0001) in CN-AML samples, and the identical results were found in AML patients receiving chemotherapy (P < 0.0001) and Allo-HSCT (P < 0.0001). RASGEF1A RNA expression level is an CN-AML patients’ independent prognostic factor (EFS: HR = 5.5534, 95% CI: 1.2982–23.756, P = 0.0208; OS: HR = 5.3615, 95% CI: 1.1014–26.099, P = 0.0376). The IC50 (half maximal inhibitory concentration) of Crenolanib of CN-AML samples with RASGEF1A high expression level is lower. In addition, patients with high RASGEF1A methylation level had significant favorable prognosis (EPS: P < 0.0001, OS: P < 0.0001). Furthermore, the integrative analysis of expression and methylation of RASGEF1A could classify CN-AML patients into subgroups with different prognosis (EFS: P < 0.0001, OS: P < 0.0001). Conclusion Higher RASGEF1A RNA expression and lower DNA methylation predicts CN-AML patients’ poorer prognosis. The RASGEF1A high expression level from patients with CN-AML have better sensitivity to Crenolanib. The integrative analysis of RASGEF1A RNA expression and DNA methylation can provide a more accurate classification for prognosis. Lower RASGEF1A expression is a favorable prognostic factor for AML patients receiving chemotherapy or Allo-HSCT.

scholarly journals DNA Methylation Changes Were Involved in Inhibiting Ethylene Signaling and Delaying Senescence of Tomato Fruit Under Low Temperature

2021 ◽  
Author(s):  
Wenhui Duan ◽  
Shiyin Xie ◽  
Hongmiao Song
Keyword(s):  
Dna Methylation ◽  
Low Temperature ◽  
Methylation Level ◽  
Cpg Island ◽  
Tomato Fruit ◽  
Ethylene Biosynthesis ◽  
Epigenetic Mechanism ◽  
Expression Level ◽  
Ethylene Signaling ◽  
Delayed Senescence

Abstract Objectives To comprehend the epigenetic mechanism of low temperature in delaying senescence of fruit, the changes of DNA methylation patterns of genes related to ethylene biosynthesis and signaling were analyzed in tomato fruit. Results In the present results, the expression level of LeEIN3, SlERF-A1 and LeERT10 decreased, and the expression level of LeCTR1 increased in tomato fruit stored at the low temperature of 11 oC. Meanwhile, the DNA methylation level of CpG island of LeEIN3, SlERF-A1 and LeERT10 increased, and the DNA methylation level of CpG island of LeCTR1 decreased in tomato fruit, respectively. The low temperature suppressed ethylene signaling via changing DNA methylation and gene expression, and delayed senescence of tomato fruit. Conclusions The present study offered valuable information for understanding the role of DNA methylation in senescence of fruit, and provided a foundation for genetic modifying the epigenetic target sites and controlling fruit senescence.

scholarly journals Analysis of DNA methylation level and mRNA expression of Transient Receptor Ankyrin Member 1 (TRPA1) in endometriosis-associated pain

2021 ◽  
pp. 1-10
Author(s):  
Ocktariyana ◽  
Nurul Hikmawati ◽  
Andon Hestiantoro ◽  
Raden Muharam ◽  
Muhammad Luky Marwali ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Methylation Level ◽  
Rating Scale ◽  
Expression Level ◽  
Pain Level ◽  
Mrna Expression Level ◽  
Significant Difference ◽  
Peritoneal Endometriosis ◽  
Transient Receptor

Transient Receptor Ankyrin Member 1 (TRPA1) is an ion channel family protein that regulates pain sensation through sensory neurons' activity. This study's purpose to analyzes the DNA methylation and mRNA expression level of the TRPA1 gene in endometriosis and its correlation with pain level. Twenty samples of peritoneal endometriosis and endometrial samples were obtained from women with endometriosis, which was subsequently compared to 20 endometrial samples of women without endometriosis. The DNA methylation level of TRPA1 was analyzed using Methylation-specific PCR (MS-PCR) and ImageJ software, while the mRNA expression of TRPA1 was analyzed using qRT-PCR. Furthermore, the pain level was measured using the numeric rating scale (NRS) by interviewing all the women. This study showed that there was a significant difference in the mRNA expression of TRPA1 in peritoneal endometriosis. The TRPA1 was unmethylated in both peritoneal and endometrial samples in endometriosis. However, DNA Methylation level of TRPA1 in peritoneal and endometrial of endometriosis compared to normal endometrial were no significant difference. Additionally, there was no correlation between DNA methylation level and mRNA expression level of TRPA1 in all samples, along with the endometriosis-associated pain.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

scholarly journals Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Wuping Yang ◽  
Kenan Zhang ◽  
Lei Li ◽  
Yawei Xu ◽  
Kaifang Ma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Level ◽  
Cell Renal Cell Carcinoma ◽  
Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

scholarly journals Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wan-Ru Wang ◽  
Nai-Tzu Chen ◽  
Nai-Yun Hsu ◽  
I-Ying Kuo ◽  
Hsin-Wen Chang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Respiratory Symptoms ◽  
Smoking Status ◽  
Phthalate Esters ◽  
Allergic Diseases ◽  
Percentage Increase ◽  
Phthalate Exposure ◽  
Settled Dust ◽  
Butyl Phthalate

Abstract Background Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases. Results Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children’s respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β =  − 1.75, p = 0.015) after adjustment for child’s sex, age, BMI, parents’ smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65–0.99). Conclusions Exposure to BBzP in settled dust might increase children’s respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.

scholarly journals Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Yu Gu ◽  
Ji-chun Ma ◽  
Xiang-mei Wen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Related Gene ◽  
Targeted Bisulfite Sequencing ◽  
Specific Pcr ◽  
Frequent Event ◽  
Acute Myeloid

Abstract Background Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated. Results In the discovery stage, we identified that DNA methylation-associated LEP expression was correlated with prognosis among obesity-related genes from the databases of The Cancer Genome Atlas. In the validation stage, we verified that LEP hypermethylation was a frequent event in AML by both targeted bisulfite sequencing and real-time quantitative methylation-specific PCR. Moreover, LEP hypermethylation, correlated with reduced LEP expression, was found to be associated with higher bone marrow blasts, lower platelets, and lower complete remission (CR) rate in AML. Importantly, survival analysis showed that LEP hypermethylation was significantly associated with shorter overall survival (OS) in AML. Moreover, multivariate analysis disclosed that LEP hypermethylation was an independent risk factor affecting CR and OS among non-M3 AML. By clinical and bioinformatics analysis, LEP may be also regulated by miR-517a/b expression in AML. Conclusions Our findings indicated that the obesity-related gene LEP methylation is associated with LEP inactivation, and acts as an independent prognostic predictor in AML.

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