Genome-Wide DNA Methylation Profile of Gene cis-Acting Element Methylations in All-trans Retinoic Acid-Induced Mouse Cleft Palate

2018 ◽  
Vol 37 (12) ◽  
pp. 993-1002 ◽  
Author(s):  
Xuan Shu ◽  
Shenyou Shu ◽  
Yuxia Zhai ◽  
Lin Zhu ◽  
Zhan Ouyang
2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 162-162
Author(s):  
Yoshiharu Matsuno ◽  
Motone Kuriyama ◽  
Hideki Fukata ◽  
Koji Sato ◽  
Chisato Mori

2008 ◽  
Vol 45 (5) ◽  
pp. 545-551 ◽  
Author(s):  
Motone Kuriyama ◽  
Akikazu Udagawa ◽  
Shinya Yoshimoto ◽  
Masaharu Ichinose ◽  
Koji Sato ◽  
...  

Objectives: The aim of this study was to analyze epigenetic (specifically, DNA methylation) participation in the mechanisms of cleft palate only induced by maternal exposure to all-trans retinoic acid in mice. Design: Cleft palate only was induced in fetuses by maternal exposure to all-trans retinoic acid. Their secondary palates were excised for analysis. Cytosine extension assay and restriction landmark genomic scanning were performed to analyze DNA methylation status. The expression levels of the DNA methyltransferases were examined by real-time reverse transcriptase–polymerase chain reaction. Results: Using cytosine extension assay, on gestation day 14.5, the status of DNA methylation within CpG islands and in global DNA was decreased significantly in all-trans retinoic acid–treated groups compared with the controls (p < .01 and p < .05). In the controls, the status within CpG islands on gestation day 14.5 was significantly increased compared with gestation days 13.5 and 18.5 (p < .01). Using real-time reverse transcriptase–polymerase chain reaction, there was no significant change in the expression of DNA methyltransferases, except on gestation day 18.5. Using restriction landmark genomic scanning on gestation day 18.5, five spots (0.49%) in the controls and one spot (0.1%) in all-trans retinoic acid–treated groups were specifically detected. Conclusions: These results indicate that changes in DNA methylation may play an important role in the manifestation of cleft palate only caused by environmental factors such as maternal exposure to all-trans retinoic acid.


Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 397 ◽  
Author(s):  
Krysta Coyle ◽  
Cheryl Dean ◽  
Margaret Thomas ◽  
Dejan Vidovic ◽  
Carman Giacomantonio ◽  
...  

All-trans retinoic acid (atRA) regulates gene expression and is used to treat acute promyelocytic leukemia. Attempts to use atRA in breast cancer without a stratification strategy have resulted in limited overall effectiveness. To identify biomarkers for the treatment of triple-negative breast cancer (TNBC) with atRA, we characterized the effects of atRA on the tumor growth of 13 TNBC cell lines. This resulted in a range of effects that was not predictable based on previously hypothesized predictors of response, such as the levels of atRA nuclear shuttling proteins fatty acid binding protein 5 (FABP5) and cellular retinoic acid binding protein 2 (CRABP2). Transcriptional profiling revealed that atRA induced distinct gene expression changes in the sensitive versus resistant cell lines that were mostly independent of the presence of retinoic acid response elements (RAREs) or peroxisome proliferator response elements (PPREs). Given the importance of DNA methylation in regulating gene expression, we hypothesized that differential DNA methylation could predict the response of TNBCs to atRA. We identified over 1400 sites that were differentially methylated between atRA resistant and sensitive cell lines. These CpG sites predicted the response of four TNBC patient-derived xenografts to atRA, and we utilized these xenografts to refine the profile and identified that as many as 17% of TNBC patients could benefit from atRA treatment. These data illustrate that differential methylation of specific CpGs may be useful biomarkers for predicting the response of patient tumors to atRA treatment.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei-Ying Zeng ◽  
Yu-Rong Tan ◽  
Sheng-Feng Long ◽  
Zu-Dong Sun ◽  
Zhen-Guang Lai ◽  
...  

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.


2020 ◽  
Author(s):  
Yuanmei Wang ◽  
Liying Liu ◽  
Min Li ◽  
Lili Lin ◽  
Pengcheng Su ◽  
...  

Abstract Background: Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses a severe threat to public health. Chicken meat and eggs are the main sources of human salmonellosis. DNA methylation is involved in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in the response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole-genome bisulfite sequencing in the current study.Results: There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean Reads and 126,782,896 unique reads in the inoculated group. The methylation density in the gene body was higher than that in the upstream and downstream regions of the gene. There were 8,946 differentially methylated genes (3,639 hypo-methylated genes, 5,307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated.Conclusions: The genome-wide DNA methylation profile in the response to SE inoculation in chicken was analyzed. SE inoculation promoted the DNA methylation in the chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play crucial roles in the methylation regulation of SE inoculation in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.


2019 ◽  
Vol 40 (5) ◽  
pp. 611-623 ◽  
Author(s):  
Takeshi Makabe ◽  
Eri Arai ◽  
Takuro Hirano ◽  
Nanako Ito ◽  
Yukihiro Fukamachi ◽  
...  

Abstract The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.


2020 ◽  
Vol 24 (15) ◽  
pp. 8753-8762
Author(s):  
Tianqi Fan ◽  
Xiangyu Meng ◽  
Chuiguo Sun ◽  
Xiaoxi Yang ◽  
Guanghui Chen ◽  
...  

2020 ◽  
Vol 88 ◽  
pp. 102483
Author(s):  
P. Suarez-Bregua ◽  
A. Pérez-Figueroa ◽  
J. Hernández-Urcera ◽  
P. Morán ◽  
J. Rotllant

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