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Fulltext Sperm epigenetics landscape: correlation with embryo quality, reproductive outcomes and offspring's health

Garrido N, Boitrelle F, Saleh R, Durairajanayagam D, Colpi G, Agarwal A

Panminerva Med, 2023 Jun;65(2):166-178.
PMID: 37335245 DOI: 10.23736/S0031-0808.23.04871-1

Epigenetics refers to how gene expression and function are modulated without modifying the DNA sequence but through subtle molecular changes or interactions with it. As spermatogenesis progresses, male germ cells suffer plenty of epigenetic modifications, resulting in the definitive epigenome of spermatozoa conditioning its functionality, and this process can be altered by several internal and external factors. The paternal epigenome is crucial for sperm function, fertilization, embryo development, and offspring's health, and altered epigenetic states are associated with male infertility with or without altered semen parameters, embryo quality impairment, and worse ART outcomes together with the future offspring's health risks mainly through intergenerational transmission of epigenetic marks. Identifying epigenetic biomarkers may improve male factor diagnosis and the development of targeted therapies, not only to improve fertility but also to allow an early detection of risk and disease prevention in the progeny. While still there is much research to be done, hopefully in the near future, improvements in high-throughput technologies applied to epigenomes will permit our understanding of the underlying epigenetic mechanisms and the development of diagnostics and therapies leading to improved reproductive outcomes. In this review, we discuss the mechanisms of epigenetics in sperm and how epigenetics behave during spermatogenesis. Additionally, we elaborate on the relationship of sperm epigenetics with sperm parameters and male infertility, and highlight the impact of sperm epigenetic alterations on sperm parameters, embryo quality, ART outcomes, miscarriage rates and offspring's health. Furthermore, we provide insights into the future research of epigenetic alterations in male infertility.

Matched MeSH terms: DNA Methylation/genetics
Fulltext Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

Aanniz T, Bouyahya A, Balahbib A, El Kadri K, Khalid A, Makeen HA, et al.

Chem Biol Interact, 2024 Apr 01;392:110907.
PMID: 38395253 DOI: 10.1016/j.cbi.2024.110907

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.

Matched MeSH terms: DNA Methylation
DNA Methylation: An Epigenetic Insight into Type 2 Diabetes Mellitus

Alam F, Islam MA, Gan SH, Mohamed M, Sasongko TH

Curr Pharm Des, 2016;22(28):4398-419.
PMID: 27229720

DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mellitus (T2DM). Current evidences indicate an association of DNA methylation with T2DM. This review provides an overview of how various factors play crucial roles in T2DM pathogenesis and how DNA methylation interacts with these factors. Additionally, an update on current techniques of DNA methylation analysis with their pros and cons is provided as a basis for the adoption of suitable techniques in future DNA methylation research towards better management of T2DM. To elucidate the mechanistic relationship between vital environmental factors and the development of T2DM, a better understanding of the changes in gene expression associated with DNA methylation at the molecular level is still needed.

Matched MeSH terms: DNA Methylation*
Fulltext DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells

Mohamed Sa'dom SAF, Raikundalia S, Shamsuddin S, See Too WC, Few LL

Genes (Basel), 2021 06 01;12(6).
PMID: 34205960 DOI: 10.3390/genes12060853

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between -225 and -56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.

Matched MeSH terms: DNA Methylation*
Fulltext Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study

Ambatipudi S, Cuenin C, Hernandez-Vargas H, Ghantous A, Le Calvez-Kelm F, Kaaks R, et al.

Epigenomics, 2016 May;8(5):599-618.
PMID: 26864933 DOI: 10.2217/epi-2016-0001

AIM: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure.
MATERIALS & METHODS: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort.
RESULTS: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation.
CONCLUSION: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.

Matched MeSH terms: DNA Methylation*
Fulltext Epigenome-wide association study of adiposity and future risk of obesity-related diseases

Campanella G, Gunter MJ, Polidoro S, Krogh V, Palli D, Panico S, et al.

Int J Obes (Lond), 2018 Dec;42(12):2022-2035.
PMID: 29713043 DOI: 10.1038/s41366-018-0064-7

BACKGROUND: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.
METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.
RESULTS: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10-8 to 3.27×10-18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10-7), higher triglyceride levels (P = 5.37×10-9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10-10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P

Matched MeSH terms: DNA Methylation/genetics*
Fulltext Persistent DNA Methylation Changes across the First Year of Life and Prenatal NO2 Exposure in a Canadian Prospective Birth Study

Lee S, Sbihi H, MacIsaac JL, Balshaw R, Ambalavanan A, Subbarao P, et al.

Environ Health Perspect, 2024 Apr;132(4):47004.
PMID: 38573328 DOI: 10.1289/EHP13034

BACKGROUND: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases.
OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure.
METHODS: Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data.
RESULTS: At birth (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations.
DISCUSSION: Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. https://doi.org/10.1289/EHP13034.

Matched MeSH terms: DNA Methylation*
Dietary Plant Metabolites Induced Epigenetic Modification as a Novel Strategy for the Management of Prostate Cancer

Singh V, Shirbhate E, Kore R, Mishra A, Johariya V, Veerasamy R, et al.

Mini Rev Med Chem, 2024;24(15):1409-1426.
PMID: 38385496 DOI: 10.2174/0113895575283895240207065454

Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy. We first outline the key epigenetic mechanisms involved in prostate cancer pathogenesis, including histone modifications, DNA methylation, and miRNA or Long Noncoding RNA (lncRNA) dysregulation. Next, we delve into the vast array of dietary plant metabolites that have demonstrated promising anti-cancer effects through epigenetic regulation. Resveratrol, minerals, isothiocyanates, curcumin, tea polyphenols, soy isoflavones and phytoestrogens, garlic compounds, anthocyanins, lycopene, and indoles are among the most extensively studied compounds. These plant-derived bioactive compounds have been shown to influence DNA methylation patterns, histone modifications, and microRNA expression, thereby altering the gene expression allied with prostate cancer progression, cell proliferation, and apoptosis. We also explore preclinical and clinical studies investigating the efficacy of dietary plant metabolites as standalone treatments or in combination with traditional treatments for people with prostate cancer. The present work highlights the potential of dietary plant metabolites as epigenetic modulators to treat prostate cancer. Continued research in this field may pave the way for personalized and precision medicine approaches, moving us closer to the goal of improved prostate cancer management.

Matched MeSH terms: DNA Methylation/drug effects
Fulltext Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities

Kafle A, Suttiprapa S, Muhammad M, Tenorio JCB, Mahato RK, Sahimin N, et al.

PLoS Negl Trop Dis, 2024 Sep;18(9):e0012477.
PMID: 39236081 DOI: 10.1371/journal.pntd.0012477

BACKGROUND: Epigenetic modifications, such as DNA methylation and histone modifications, are pivotal in regulating gene expression pathways related to inflammation and cancer. While there is substantial research on epigenetic markers in cholangiocarcinoma (CCA), Opisthorchis viverrini-induced cholangiocarcinoma (Ov-CCA) is overlooked as a neglected tropical disease (NTD) with limited representation in the literature. Considering the distinct etiological agent, pathogenic mechanisms, and pathological manifestations, epigenetic research plays a pivotal role in uncovering markers and potential targets related to the cancer-promoting and morbidity-inducing liver fluke parasite prevalent in the Great Mekong Subregion (GMS). Emerging studies highlight a predominant hypermethylation phenotype in Opisthorchis viverrini (O. viverrini) tumor tissues, underscoring the significance of abnormal DNA methylation and histone modifications in genes and their promoters as reliable targets for Ov-CCA.
PRINCIPAL FINDINGS: Relevant published literature was identified by searching major electronic databases using targeted search queries. This process retrieved a total of 81 peer-reviewed research articles deemed eligible for inclusion, as they partially or fully met the pre-defined selection criteria. These eligible articles underwent a qualitative synthesis and were included in the scoping review. Within these, 11 studies specifically explored Ov-CCA tissues to investigate potential epigenetic biomarkers and therapeutic targets. This subset of 11 articles provided a foundation for exploring the applications of epigenetics-based therapies and biomarkers for Ov-CCA. These articles delved into various epigenetic modifications, including DNA methylation and histone modifications, and examined genes with aberrant epigenetic changes linked to deregulated signalling pathways in Ov-CCA progression.
CONCLUSIONS: This review identified epigenetic changes and Wnt/β-catenin pathway deregulation as key drivers in Ov-CCA pathogenesis. Promoter hypermethylation of specific genes suggests potential diagnostic biomarkers and dysregulation of Wnt/β-catenin-modulating genes contributes to pathway activation in Ov-CCA progression. Reversible epigenetic changes offer opportunities for dynamic disease monitoring and targeted interventions. Therefore, this study underscores the importance of these epigenetic modifications in Ov-CCA development, suggesting novel therapeutic targets within disrupted signalling networks. However, additional validation is crucial for translating these novel insights into clinically applicable strategies, enhancing personalised Ov-CCA management approaches.

Matched MeSH terms: DNA Methylation*
Fulltext Complete Genome Sequence and Methylome Analysis of Aeromonas hydrophila Strain YL17, Isolated from a Compost Pile

Lim YL, Roberts RJ, Ee R, Yin WF, Chan KG

Genome Announc, 2016 Mar 03;4(2).
PMID: 26941143 DOI: 10.1128/genomeA.00060-16

In this report, we announce the complete genome sequence of Aeromonas hydrophila strain YL17. Single-molecule real-time (SMRT) DNA sequencing was used to generate the complete genome sequence and the genome-wide DNA methylation profile of this environmental isolate. A total of five unique DNA methyltransferase recognition motifs were reported here.

Matched MeSH terms: DNA Methylation
Fulltext Epigenetic changes of DRD2 gene in Pathogenesis of Schizophrenia

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):3-3.
MyJurnal

The dopamine hypothesis has earlier dominated the theories for the
development of schizophrenia based on the early pharmacologic evidence. The
antipsychotic drugs, among others, is thought to interfere with the function of the
dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence
suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia.
Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is
insufficient mainly due to the poor accessibility and limited brain samples. Of late, new
data has suggested the global impact of DNA methylation in the development of
schizophrenia, thus methylation in the peripheral blood could infer changes in the brain.
The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of
schizophrenia.

Matched MeSH terms: DNA Methylation
Comparative sequence and methylation analysis of chloroplast and amyloplast genomes from rice

Muniandy K, Tan MH, Song BK, Ayub Q, Rahman S

Plant Mol Biol, 2019 May;100(1-2):33-46.
PMID: 30788769 DOI: 10.1007/s11103-019-00841-x

KEY MESSAGE: Grain amyloplast and leaf chloroplast DNA sequences are identical in rice plants but are differentially methylated. The leaf chloroplast DNA becomes more methylated as the rice plant ages. Rice is an important crop worldwide. Chloroplasts and amyloplasts are critical organelles but the amyloplast genome is poorly studied. We have characterised the sequence and methylation of grain amyloplast DNA and leaf chloroplast DNA in rice. We have also analysed the changes in methylation patterns in the chloroplast DNA as the rice plant ages. Total genomic DNA from grain, old leaf and young leaf tissues were extracted from the Oryza sativa ssp. indica cv. MR219 and sequenced using Illumina Miseq. Sequence variant analysis revealed that the amyloplast and chloroplast DNA of MR219 were identical to each other. However, comparison of CpG and CHG methylation between the identical amyloplast and chloroplast DNA sequences indicated that the chloroplast DNA from rice leaves collected at early ripening stage was more methylated than the amyloplast DNA from the grains of the same plant. The chloroplast DNA became more methylated as the plant ages so that chloroplast DNA from young leaves was less methylated overall than amyloplast DNA. These differential methylation patterns were primarily observed in organelle-encoded genes related to photosynthesis followed by those involved in transcription and translation.

Matched MeSH terms: Methylation
Fulltext Methylation Profile of Cancer Testis Antigens in Colorectal Cancer

Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.

Iran J Immunol, 2023 Mar 14;20(1):83-91.
PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171

BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.
OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.
METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.
RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.
CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.

Matched MeSH terms: Methylation
DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients

Nour El Huda AR, Norsidah KZ, Nabil Fikri MR, Hanisah MN, Kartini A, Norlelawati AT

Psychiatry Clin Neurosci, 2018 Apr;72(4):266-279.
PMID: 29160620 DOI: 10.1111/pcn.12622

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.
METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.
RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P

Matched MeSH terms: DNA Methylation/drug effects; DNA Methylation/physiology*
Fulltext A new 4alpha-methylated sterol from a Nephthea sp. (Nephtheidae) Bornean soft coral

Ishii T, Matsuura H, Zhaoqi Z, Vairappan CS

Molecules, 2009;14(9):3360-6.
PMID: 19783930 DOI: 10.3390/molecules14093360

A new 4alpha-methyl sterol, 4alpha-methyl-ergosta-6,8(14),22E-triene-3beta-ol (1), was isolated along with cholesterol from a Nephthea sp. Bornean soft coral The structure of compound 1 was elucidated on the basis of spectroscopic analysis and comparison of the data with those of the related compounds.

Matched MeSH terms: Methylation
Epigenetics: The master control of endothelial cell fate in cancer

V Subramaniam A, Yehya AHS, Cheng WK, Wang X, Oon CE

Life Sci, 2019 Sep 01;232:116652.
PMID: 31302197 DOI: 10.1016/j.lfs.2019.116652

The development of new blood vessels from pre-existing vasculature is called angiogenesis. The growth of tumors depends on a network of supplying vessels that provide them with oxygen and nutrients. Pro-angiogenic factors that are secreted by tumors will trigger the sprouting of nearby existing blood vessels towards themselves and therefore researchers have developed targeted therapy towards these pro-angiogenic proteins to inhibit angiogenesis. However, certain pro-angiogenic proteins tend to bypass the inhibition. Thus, instead of targeting these expressed proteins, research towards angiogenesis inhibition had been focused on a deeper scale, epigenetic modifications. Epigenetic regulatory mechanisms are a heritable change in a sequence of stable but reversible gene function modification yet do not affect the DNA primary sequence directly. Methylation of DNA, modification of histone and silencing of micro-RNA (miRNA)-associated gene are currently considered to initiate and sustain epigenetic changes. Recent findings on the subject matter have provided an insight into the mechanism of epigenetic modifications, thus this review aims to present an update on the latest studies.

Matched MeSH terms: DNA Methylation
Signatures of gene expression, DNA methylation and microRNAs of hepatocellular carcinoma with vascular invasion

Sulaiman SA, Abu N, Ab-Mutalib NS, Low TY, Jamal R

Future Oncol, 2019 Aug;15(22):2603-2617.
PMID: 31339048 DOI: 10.2217/fon-2018-0909

Aim: Micro and macro vascular invasion (VI) are known as independent predictors of tumor recurrence and poor survival after surgical treatment of hepatocellular carcinoma (HCC). Here, we aimed to re-analyze The Cancer Genome Atlas of liver hepatocellular carcinoma datasets to identify the VI-expression signatures. Materials & methods: We filtered The Cancer Genome Atlas liver hepatocellular carcinoma (LIHC) datasets into three groups: no VI (NVI = 198); micro VI (MIVI = 89) and macro VI (MAVI = 16). We performed differential gene expression, methylation and microRNA analyses. Results & conclusion: We identified 12 differentially expressed genes and 55 differentially methylated genes in MAVI compared with no VI. The GPD1L gene appeared in all of the comparative analyses. Higher GPD1L expression was associated with VI and poor outcomes in the HCC patients.

Matched MeSH terms: Methylation
Silencing of transgene expression in mammalian cells by DNA methylation and histone modifications in gene therapy perspective

Alhaji SY, Ngai SC, Abdullah S

Biotechnol Genet Eng Rev, 2019 Apr;35(1):1-25.
PMID: 30514178 DOI: 10.1080/02648725.2018.1551594

DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.

Matched MeSH terms: DNA Methylation
Fulltext Prediction of clinical symptoms of Schizophrenia based on COMT Methylation marker

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):19-19.
MyJurnal

The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic
state is involved in causing psychosis and antipsychotic drugs block the
dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter
dopamine in the synapses and plays a role in the neurocognitive function. The
dysregulation of dopamine in the prefrontal cortex influences the cognitive function and
the severity of the psychotic symptoms in schizophrenia. During epigenetic event,
methylated COMT gene may cause reduction in its expression and contribute to the
clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the
feasibility of using COMT DNA methylation for the prediction of specific psychotic
presentation of schizophrenia. (Copied from article).

Matched MeSH terms: DNA Methylation
Fulltext Expression and DNA methylation of SERK, BBM, LEC2 and WUS genes in in vitro cultures of Boesenbergia rotunda (L.) Mansf

Karim R, Tan YS, Singh P, Khalid N, Harikrishna JA

Physiol Mol Biol Plants, 2018 Sep;24(5):741-751.
PMID: 30150851 DOI: 10.1007/s12298-018-0566-8

The process of somatic embryogenesis and plant regeneration involve changes in gene expression and have been associated with changes in DNA methylation. Here, we report the expression and DNA methylation patterns of SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK), BABY BOOM (BBM), LEAFY COTYLEDON 2 (LEC2) and WUSCHEL (WUS) in meristematic block of newly emerged shoots from rhizome, embryogenic and non-embryogenic calli, prolonged cell suspension culture, ex vitro leaf, and in vitro leaf of regenerated plants of Boesenbergia rotunda. Among all seven samples, based on qRT-PCR, the highest level of expression of SERK, BBM and LEC2 was in embryogenic callus, while WUS was most highly expressed in meristematic block tissue followed by embryogenic callus. Relatively lower expression was observed in cell suspension culture and watery callus for SERK, LEC2 and WUS and in in vitro leaf for BBM. For gene specific methylation determined by bisulfite sequencing data, embryogenic callus samples had the lowest levels of DNA methylation at CG, CHG and CHH contexts of SERK, LEC2 and WUS. We observed negative correlation between DNA methylation at the CG and CHG contexts and the expression levels of SERK, BBM, LEC2 and WUS. Based on our results, we suggest that relatively higher expression and lower level of DNA methylation of SERK, BBM, LEC2 and WUS are associated with somatic embryogenesis and plant regeneration in B. rotunda.

Matched MeSH terms: DNA Methylation

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