scholarly journals Effects of cytochalasin B on DNA methylation and histone modification in parthenogenetically activated porcine embryos

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 519-527 ◽  
Author(s):  
Xiaoxiao Hou ◽  
Jun Liu ◽  
Zhiren Zhang ◽  
Yanhui Zhai ◽  
Yutian Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Histone Modification ◽  
Actin Polymerization ◽  
Cytochalasin B ◽  
Epigenetic Modification ◽  
Cell Activity ◽  
Cleavage Rate ◽  
Expression Levels ◽  
Mammalian Embryos

DNA methylation and histone modification play important roles in the development of mammalian embryos. Cytochalasin B (CB) is an actin polymerization inhibitor that can significantly affect cell activity and is often used in studies concerning cytology. In recent years, CB is also commonly being used inin vitroexperiments on mammalian embryos, but few studies have addressed the effect of CB on the epigenetic modification of embryonic development, and the mechanism underlying this process is also unknown. This study was conducted to investigate the effects of CB on DNA methylation and histone modification in the development of parthenogenetically activated porcine embryos. Treatment with 5 μg/mL CB for 4 h significantly increased the cleavage rate, blastocyst rate and total cell number of blastocysts. However, the percentage of apoptotic cells and the expression levels of the apoptosis-related genesBCL-XL,BAXandCASP3were significantly decreased. Treatment with CB significantly decreased the expression levels ofDNMT1,DNMT3a,DNMT3b,HAT1andHDAC1at the pronuclear stage and promoted the conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). After CB treatment, the level of AcH3K9 was upregulated and the level of H3K9me3 was downregulated. When combined with Scriptaid and 5-Aza-Cdr, CB further improved the embryonic development competence and decreased the expression ofBCL-XL,BAXandCASP3. In conclusion, these results suggest that CB could improve embryonic development and the quality of the blastocyst by improving the epigenetic modification during the development of parthenogenetically activated embryos.

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

scholarly journals Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6039
Author(s):  
Bo Xu ◽  
Hao Wang ◽  
Li Tan
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Epigenetic Modification ◽  
Current Understanding ◽  
Future Perspectives ◽  
Cancer Hallmarks ◽  
The Past

DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.

Programming and Inheritance of Parental DNA Methylomes in Vertebrates

Physiology ◽  
2015 ◽  
Vol 30 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Weimin Ci ◽  
Jiang Liu
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Epigenetic Modification ◽  
Early Embryogenesis ◽  
Recent Advances

5-Methylcytosine (5mC) is a major epigenetic modification in animals. The programming and inheritance of parental DNA methylomes ensures the compatibility for totipotency and embryonic development. In vertebrates, the DNA methylomes of sperm and oocyte are significantly different. During early embryogenesis, the paternal and maternal methylomes will reset to the same state. Herein, we focus on recent advances in how offspring obtain the DNA methylation information from parents in vertebrates.

scholarly journals Epigenetic: A new approach to etiology of infertility

2017 ◽  
Vol 25 (4) ◽  
pp. 255-62
Author(s):  
Silvia W. Lestari ◽  
Meidika D. Rizki
Keyword(s):  
Dna Methylation ◽  
Histone Modification ◽  
Histone Methylation ◽  
Complex Disease ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
New Approach ◽  
Male And Female ◽  
Germinal Cells ◽  
Embryonic Death

Infertility is a complex disease which could be caused by male and female factors. The etiology from both factors needs further study. There are some approaches to understanding the etiology of infertility, one of them is epigenetic. Epigenetic modifications consist of DNA methylation, histone modifications, and chromatin remodelling. Male and female germinal cells undergo epigenetic modifications dynamically during differentiation into matured sperm and oocyte cells. In a male, the alteration of DNA methylation in spermatogenesis will cause oligo/asthenozoospermia. In addition, the histone methylation, acetylation, or other histone modification may lead sperm lose its ability to fertilize oocyte. Similarly, in a female, the alteration of DNA methylation and histone modification affects oogenesis, created aneuploidy in fertilized oocytes and resulted in embryonic death in the uterus. Alteration of these epigenetic modification patterns will cause infertility, both in male and female.

scholarly journals COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding

2021 ◽  
pp. 00802-2020
Author(s):  
Sai Sneha Priya Nemani ◽  
Cornelis Joseph Vermeulen ◽  
Martin Pech ◽  
Alen Faiz ◽  
Brian George G. Oliver ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Sequencing ◽  
Airway Epithelium ◽  
Epigenetic Modification ◽  
Healthy Controls ◽  
Expression Levels ◽  
Asthmatic Airway ◽  
Bronchial Biopsies ◽  
Bead Arrays

BackgroundReduction of COL4A3 in asthmatic airways, one of the six isoforms of collagen 4 results in increased inflammation and angiogenesis implicating it as a central part of asthma pathogenesis. However, the path underlying these diminished COL4A3 levels has been elusive to date. This study investigated a possible mechanism underlying the reduction of COL4A3 expression.MethodsBronchial biopsies of n=76 asthmatics and n=83 controls were subjected to RNA-sequencing and DNA methylation bead arrays to identify expression and methylation changes. The binding of ZNF263 was analysed by ChiP-Seq coupled with qPCR. Effects of ZNF263 silencing, using siRNA, on the COL4A3 expression were studied by qPCR.ResultsCOL4A3 expression was significantly reduced in bronchial biopsies compared to healthy controls whereas DNA methylation levels at cg11797365 were increased. COL4A3 expression levels were significantly low in asthmatics without ICS use whereas the expression was not statistically different between asthmatics using ICS and controls. Methylation levels at cg11797365 in vitro were increased upon consecutive rhinovirus infections.ConclusionOur data indicates an epigenetic modification as a contributing factor for the loss of COL4A3 expression in asthmatic airway epithelium.

DNA methylation of the TAA1 gene regulates formation of the pollen wall in chemically induced male sterility in wheat (Triticum aestivum)

2017 ◽  
Vol 68 (9) ◽  
pp. 817
Author(s):  
Guiping Li ◽  
Qingsong Ba ◽  
Gaisheng Zhang ◽  
Lanlan Zhang ◽  
Chu Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Triticum Aestivum ◽  
Male Sterility ◽  
Epigenetic Modification ◽  
Core Promoter ◽  
Pollen Wall ◽  
Pcr Analysis ◽  
Tetradecanoic Acid ◽  
Expression Levels ◽  
Chemically Induced

DNA methylation is an important epigenetic modification that may contribute to environmentally induced phenotypic variations by regulating gene expression. Chemically induced male sterility (CIMS) lines in wheat (Triticum aestivum L.) can transform from sterile to fertile, induced by a chemical hybridising agent during anther development. So far, little is known about the DNA methylation variation of CIMS in wheat. TAA1 regulates pollen wall development, probably through converting fatty acids to fatty alcohol in wheat. We investigated the DNA methylation pattern of the TAA1 gene in the core promoter region by using the bisulfite genomic sequencing method, and higher methylation was observed in CIMS. The expression levels of the TAA1 gene were also evaluated by real time quantitative reverse transcriptase PCR analysis, which revealed that the expression levels of the TAA1 gene were downregulated in CIMS. The aliphatic composition of the anther underwent accumulation in line 1376-CIMS, revealed by gas chromatography–mass spectrometry, including increments of tetradecanoic acid, hexadecanoic acid and octadecanoic acid. Scanning electron microscopy revealed that anther and pollen wall formation was significantly altered in 1376-CIMS.These results suggested that DNA methylation of the TAA1 gene may be involved in the sterility–fertility transition of CIMS.

85 Regulation of mammalian target of rapamycin signaling post-fertilisation is essential for efficient development of bovine pre-implantation embryos

2020 ◽  
Vol 32 (2) ◽  
pp. 169
Author(s):  
M. El Sheikh ◽  
A. Mesalam ◽  
A. Mesalam ◽  
K. Lee ◽  
I. Kong
Keyword(s):  
Embryonic Development ◽  
Laser Scanning ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Confocal Laser ◽  
Blastocyst Development ◽  
Cleavage Rate ◽  
Dapi Staining ◽  
Expression Levels

The phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is considered a key regulator of various cellular responses related to growth, proliferation, survival, apoptosis, and autophagy. The expression of mTOR in cumulus cells and all oocyte stages highlights a role in embryonic development, but its function in the context of embryo development is not completely clarified. In the current study, we investigated the effect of mTOR activation on the total cleavage and blastocyst development rates in bovine. Oocytes collected from bovine ovaries were invitro matured (around 50 oocytes per group) and fertilised before incubation with the mTOR activator MHY1485 (1 µM) for 72h at 38.5°C and 5% CO2. The total cleavage rate at Day 4 post-fertilisation and the blastocyst development rate at Day 8 post-fertilisation were recorded. The expression levels of the mTOR and PI3K in Day 8 blastocysts were investigated using immunofluorescence and imaged using confocal laser-scanning microscope, whereas the fluorescence intensity was analysed using ImageJ software. The difference between groups was analysed using Student's t-test (GraphPad Prism). Results of microscopic investigations showed higher rates of Day 4 cleavage (83.7±1.3 vs. 72±0.8% for control) and Day 8 blastocyst development (40.4±1.7 vs. 33±1.8% for control) upon addition of MHY1485 (P<0.05). The immunofluorescence showed higher mTOR and PI3K expression levels in MHY1485-treated group than the untreated control (P<0.05). The total number of cells per blastocyst, using 4′,6-diamidino-2-phenylindole (DAPI) staining of the nuclei, was higher in the mTOR-activated group (194.9±4.8 vs. 171.3±3.5 for control). In conclusion, our data reflect the essential role of the mTOR signaling for bovine pre-implantation embryonic development.

scholarly journals Epigenetic modification mechanisms involved in keloid: current status and prospect

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenchang Lv ◽  
Yuping Ren ◽  
Kai Hou ◽  
Weijie Hu ◽  
Yi Yi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Expression Profiles ◽  
Critical Role ◽  
Experimental Studies ◽  
Current Status ◽  
Limited Effectiveness ◽  
External Risk ◽  
Cellular Components

AbstractKeloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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