Aberrant levels of DNA methylation and H3K9 acetylation in the testicular cells of crossbred cattle‐yak showing infertility

The mechanisms of homocysteine-mediated cardiac threats are poorly understood. Homocysteine, being the precursor to S-adenosyl methionine (a methyl donor) through methionine, is indirectly involved in methylation phenomena for DNA, RNA, and protein. We reported previously that cardiac-specific deletion of N-methyl-d-aspartate receptor-1 (NMDAR1) ameliorates homocysteine-posed cardiac threats, and in this study, we aim to explore the role of NMDAR1 in epigenetic mechanisms of heart failure, using cardiomyocytes during hyperhomocysteinemia (HHcy). High homocysteine levels activate NMDAR1, which consequently leads to abnormal DNA methylation vs. histone acetylation through modulation of DNA methyltransferase 1 (DNMT1), HDAC1, miRNAs, and MMP9 in cardiomyocytes. HL-1 cardiomyocytes cultured in Claycomb media were treated with 100 μM homocysteine in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence and presence of homocysteine at 10 μM in a dose-dependent manner. The expression of DNMT1, histone deacetylase 1 (HDAC1), NMDAR1, microRNA (miR)-133a, and miR-499 was assessed by real-time PCR as well as Western blotting. Methylation and acetylation levels were determined by checking 5′-methylcytosine DNA methylation and chromatin immunoprecipitation. Hyperhomocysteinemic mouse models (CBS+/−) were used to confirm the results in vivo. In HHcy, the expression of NMDAR1, DNMT1, and matrix metalloproteinase 9 increased with increase in H3K9 acetylation, while HDAC1, miR-133a, and miR-499 decreased in cardiomyocytes. Similar results were obtained in heart tissue of CBS+/− mouse. High homocysteine levels instigate cardiovascular remodeling through NMDAR1, miR-133a, miR-499, and DNMT1. A decrease in HDAC1 and an increase in H3K9 acetylation and DNA methylation are suggestive of chromatin remodeling in HHcy.

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Oocyte vitrification induces loss of DNA methylation and histone acetylation in the resulting embryos derived using ICSI in dromedary camel

Zygote ◽

10.1017/s0967199421000150 ◽

2021 ◽

pp. 1-10

Author(s):

F. Moulavi ◽

I.M. Saadeldin ◽

A.A. Swelum ◽

F. Tasdighi ◽

H. Hosseini-Fahraji ◽

...

Keyword(s):

Dna Methylation ◽

Blastocyst Stage ◽

Epigenetic Reprogramming ◽

Developmental Competence ◽

Oocyte Cryopreservation ◽

Dromedary Camel ◽

Cleavage Rate ◽

Oocyte Vitrification ◽

Preimplantation Embryo Development ◽

H3k9 Acetylation

Summary Oocyte cryopreservation has become an important component of assisted reproductive technology with increasing implication in female fertility preservation and animal reproduction. However, the possible adverse effects of oocyte cryopreservation on epigenetic status of the resulting embryos is still an open question. This study evaluated the effects of MII-oocyte vitrification on gene transcripts linked to epigenetic reprogramming in association with the developmental competence and epigenetic status of the resulting embryos at 2-cell and blastocyst stages in dromedary camel. The cleavage rate of vitrified oocytes following intracytoplasmic sperm injection was significantly increased compared with the control (98.2 ± 2 vs. 72.7 ± 4.1%, respectively), possibly due to the higher susceptibility of vitrified oocytes to spontaneous activation. Nonetheless, the competence of cleaved embryos derived from vitrified oocytes for development to the blastocyst and hatched blastocyst was significantly reduced compared with the control (7.7 ± 1.2 and 11.1 ± 11.1 compared with 28.1 ± 2.6 and 52.4 ± 9.9%, respectively). The relative transcript abundances of epigenetic reprogramming genes DNMT1, DNMT3B, HDAC1, and SUV39H1 were all significantly reduced in vitrified oocytes relative to the control. Evaluation of the epigenetic marks showed significant reductions in the levels of DNA methylation (6.1 ± 0.3 vs. 9.9 ± 0.5, respectively) and H3K9 acetylation (7.8 ± 0.2 vs. 10.7 ± 0.3, respectively) in 2-cell embryos in the vitrification group relative to the control. Development to the blastocyst stage partially adjusted the effects that oocyte vitrification had on the epigenetic status of embryos (DNA methylation: 4.9 ± 0.4 vs. 6.2 ± 0.6; H3K9 acetylation: 5.8 ± 0.3 vs. 8 ± 0.9, respectively). To conclude, oocyte vitrification may interfere with the critical stages of epigenetic reprogramming during preimplantation embryo development.

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Glucocorticoid Programming of the Fetal Male Hippocampal Epigenome

Endocrinology ◽

10.1210/en.2012-1980 ◽

2013 ◽

Vol 154 (3) ◽

pp. 1168-1180 ◽

Cited By ~ 62

Author(s):

Ariann Crudo ◽

Matthew Suderman ◽

Vasilis G. Moisiadis ◽

Sophie Petropoulos ◽

Alisa Kostaki ◽

...

Keyword(s):

Dna Methylation ◽

Promoter Methylation ◽

Plasma Cortisol ◽

Late Gestation ◽

Gene Promoters ◽

Fetal Plasma ◽

Genome Wide ◽

Organ Systems ◽

Increased Risk ◽

H3k9 Acetylation

Abstract The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring. Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus. Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term∼GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3–4/gp). We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation. Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated. However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated. These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation. This is important given the widespread use of sGC in the management of women in preterm labor.

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Genome-Wide DNA Methylome and Transcriptome Analysis of Porcine Testicular Cells Infected With Transmissible Gastroenteritis Virus

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.779323 ◽

2022 ◽

Vol 8 ◽

Author(s):

Jiayun Wu ◽

Xiaoru Shi ◽

Lisi Wu ◽

Zhengchang Wu ◽

Shenglong Wu ◽

...

Keyword(s):

Dna Methylation ◽

Ribosome Biogenesis ◽

Transmissible Gastroenteritis Virus ◽

Whole Genome Analysis ◽

Testicular Cells ◽

Gastroenteritis Virus ◽

Expression Of Genes ◽

Suckling Piglets ◽

Transmissible Gastroenteritis ◽

Methylation Patterns

Transmissible gastroenteritis virus (TGEV) is a porcine pathogen causing highly communicable gastrointestinal infection that are lethal for suckling piglets. In an attempt to delineate the pathogenic mechanism of TGEV-infected porcine testicular cells (ST cells), we conducted a whole genome analysis of DNA methylation and expression in ST cells through reduced bisulfate-seq and RNA-seq. We examined alterations in the methylation patterns and recognized 1764 distinct methylation sites. 385 differentially expressed genes (DEGs) were enriched in the viral defense and ribosome biogenesis pathways. Integrative analysis identified two crucial genes (EMILIN2, RIPOR3), these two genes expression were negatively correlated to promoter methylation. In conclusion, alterations in DNA methylation and differential expression of genes reveal that their potential functional interactions in TGEV infection. Our data highlights the epigenetic and transcriptomic landscapes in TGEV-infected ST cells and provides a reliable dataset for screening TGEV resistance genes and genetic markers.

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

Author(s):

Claire Francastel ◽

Frédérique Magdinier

Keyword(s):

Dna Methylation ◽

Human Genome ◽

Repetitive Dna ◽

Dna Sequences ◽

Satellite Repeats ◽

Tremendous Progress ◽

Genes Encoding ◽

Dna Elements ◽

Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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