DNA methylation is correlated with gene expression during early pregnancy in Bos taurus

Coordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A nonreceptive uterine environment may be a key contributor to pregnancy loss, as the majority of pregnancy losses occur prior to embryo implantation. DNA methylation has been highlighted as a potential contributor in regulating early pregnancy events in the uterus. It was hypothesized that DNA methylation regulates expression of key genes in the uterus during pregnancy. The correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and subfertile dairy cow strains were obtained at day 17 of pregnancy or the reproductive cycle. Microarrays were used to characterize genome-wide DNA methylation profiles and data compared with previously published transcription profiles. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. Correlations among gene expression and DNA methylation were assessed, and the 1,000 most significant correlations used for subsequent analysis. Of these, 52% percent were negatively correlated with gene expression. When this gene list was compared with previously reported gene expression studies on the same tissues, 42% were differentially expressed when pregnant and cycling animals were compared, and 11% were differentially expressed when pregnant fertile and subfertile animals were compared. DNA methylation status was correlated with gene expression in several pathways implicated in early pregnancy events. Although these data do not provide direct evidence of a causative association between DNA methylation and gene expression, this study provides critical support for an effect of DNA methylation in early pregnancy events and highlights candidate genes for future studies.

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Epigenetic Changes During Mechanically Induced Osteogenic Lineage Commitment

Journal of Biomechanical Engineering ◽

10.1115/1.4029551 ◽

2015 ◽

Vol 137 (2) ◽

Cited By ~ 14

Author(s):

Julia C. Chen ◽

Mardonn Chua ◽

Raymond B. Bellon ◽

Christopher R. Jacobs

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Shear Stress ◽

Fluid Shear Stress ◽

Methylation Status ◽

Lineage Commitment ◽

Fluid Shear ◽

Osteogenic Lineage ◽

Osteogenic Markers ◽

Heterochromatin Structure

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.

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Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

BMC Medical Genomics ◽

10.1186/s12920-021-00966-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xiao-Liang Xing ◽

Zhi-Yong Yao ◽

Chaoqun Xing ◽

Zhi Huang ◽

Jing Peng ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Risk Assessment ◽

Dna Methylation ◽

Differentially Expressed Genes ◽

Risk Score ◽

Immune Cells ◽

Assessment Model ◽

Differentially Expressed ◽

Risk Assessment Model

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

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Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.40 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Jessilyn Dunn ◽

Haiwei Qiu ◽

Soyeon Kim ◽

Daudi Jjingo ◽

Ryan Hoffman ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

Methylation Status ◽

Western Diet ◽

Dependent Manner ◽

Gene Promoters ◽

Genome Wide ◽

Methylation Patterns ◽

Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

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Comparative gene expression profile and DNA methylation status in diabetic patients of Kazak and Han people

Medicine ◽

10.1097/md.0000000000011982 ◽

2018 ◽

Vol 97 (36) ◽

pp. e11982 ◽

Cited By ~ 1

Author(s):

Cuizhe Wang ◽

Xiaodan Ha ◽

Wei Li ◽

Peng Xu ◽

Zhiwei Zhang ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Gene Expression Profile ◽

Expression Profile ◽

Methylation Status ◽

Diabetic Patients

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Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation

Toxics ◽

10.3390/toxics9120338 ◽

2021 ◽

Vol 9 (12) ◽

pp. 338

Author(s):

Karin Engström ◽

Yumjirmaa Mandakh ◽

Lana Garmire ◽

Zahra Masoumi ◽

Christina Isaxon ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Air Pollution ◽

Early Pregnancy ◽

Late Onset ◽

Dispersion Model ◽

Ambient Air ◽

Ambient Air Pollution ◽

Dna Hypomethylation ◽

Increased Risk

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants’ residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.

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Comparative functional genomic analysis of Alzheimer’s affected and naturally aging brains

PeerJ ◽

10.7717/peerj.8682 ◽

2020 ◽

Vol 8 ◽

pp. e8682

Author(s):

Yi-Shian Peng ◽

Chia-Wei Tang ◽

Yi-Yun Peng ◽

Hung Chang ◽

Chien-Lung Chen ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Microarray Data ◽

Gene List ◽

Amyloid Β ◽

Differentially Expressed ◽

Gene Expression Microarray ◽

Expression Microarray ◽

Functional Genomic Analysis ◽

Gene Expression Microarray Data

Background Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-β (Aβ) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. Methods Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. Results Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 “ALZ-only” differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.

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Title Page Title: The role of DNA methylation in the accumulation of iridoid glycosides in Rehmannia glutinosa

10.21203/rs.3.rs-403607/v1 ◽

2021 ◽

Author(s):

Tianyu Dong ◽

Xiaoyan Wei ◽

Qianting Qi ◽

Peilei Chen ◽

Yanqing Zhou ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Secondary Metabolites ◽

Iridoid Glycosides ◽

Methylation Status ◽

Plant Secondary Metabolites ◽

Dna Demethylation ◽

Terpene Biosynthesis ◽

The Relationship

Abstract Background: Epigenetic regulation plays a significant role in the accumulation of plant secondary metabolites. The terpenoids are the most abundant in the secondary metabolites of plants, iridoid glycosides belong to monoterpenoids which is one of the main medicinal components of R.glutinosa. At present, study on iridoid glycosides mainly focuses on its pharmacology, accumulation and distribution, while the mechanism of its biosynthesis and the relationship between DNA methylation and plant terpene biosynthesis are seldom reports. Results: The research showed that the expression of DXS, DXR, 10HGO, G10H, GPPS and accumulation of iridoid glycosides increased at first and then decreased with the maturity of R.glutinosa, and under different concentrations of 5-azaC, the expression of DXS, DXR, 10HGO, G10H, GPPS and the accumulation of total iridoid glycosides were promoted, the promotion effect of low concentration (15μM-50μM) was more significant, the content of genomic DNA 5mC decreased significantly, the DNA methylation status of R.glutinosa genomes was also changed. DNA demethylation promoted gene expression and increased the accumulation of iridoid glycosides, but excessive demethylation inhibited gene expression and decreased the accumulation of iridoid glycosides. Conclusion: The analysis of DNA methylation, gene expression, and accumulation of iridoid glycoside provides insights into accumulation of terpenoids in R.glutinosa and lays a foundation for future studies on the effects of epigenetics on the synthesis of secondary metabolites.

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Regulation of adenosine A2Areceptor gene expression in a model of binge eating in the amygdaloid complex of female rats

Journal of Psychopharmacology ◽

10.1177/0269881119845798 ◽

2019 ◽

Vol 33 (12) ◽

pp. 1550-1561 ◽

Cited By ~ 12

Author(s):

Maria Vittoria Micioni Di Bonaventura ◽

Mariangela Pucci ◽

Maria Elena Giusepponi ◽

Adele Romano ◽

Catia Lambertucci ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Binge Eating ◽

Epigenetic Regulation ◽

Methylation Status ◽

Amygdaloid Complex ◽

Female Rats ◽

Control Group ◽

Compensatory Mechanism ◽

Mrna Levels

Background:Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited.Methods and aims:Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2AAdenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes.Results:Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.Conclusion:We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.

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Infection with Human Immunodeficiency Virus Type 1 Upregulates DNA Methyltransferase, Resulting in De Novo Methylation of the Gamma Interferon (IFN-γ) Promoter and Subsequent Downregulation of IFN-γ Production

Molecular and Cellular Biology ◽

10.1128/mcb.18.9.5166 ◽

1998 ◽

Vol 18 (9) ◽

pp. 5166-5177 ◽

Cited By ~ 118

Author(s):

Judy A. Mikovits ◽

Howard A. Young ◽

Paula Vertino ◽

Jean-Pierre J. Issa ◽

Paula M. Pitha ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

De Novo ◽

Methylation Status ◽

Immunodeficiency Virus ◽

Ifn Γ ◽

Hiv 1 ◽

De Novo Methylation

ABSTRACT The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12, tumor necrosis factor alpha, and gamma interferon (IFN-γ), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-γ, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-γ gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV-1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-γ gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-γ gene, and increased IFN-γ production, demonstrating a direct link between methyltransferase and IFN-γ gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-γ gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals.

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