Journal Description
Epigenomes
Epigenomes
is an international, peer-reviewed, open access journal on epigenetics and epigenomics, published quarterly online by MDPI. The Epigenetics Society is affiliated with Epigenomes and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PMC, PubMed, Embase, PubAg, CAPlus / SciFinder, and other databases.
- Journal Rank: CiteScore - Q2 (Biochemistry, Genetics and Molecular Biology (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.7 days after submission; acceptance to publication is undertaken in 3.9 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
2.5 (2023);
5-Year Impact Factor:
2.3 (2023)
Latest Articles
Epigenetic Landscape of DNA Methylation in Pancreatic Ductal Adenocarcinoma
Epigenomes 2024, 8(4), 41; https://doi.org/10.3390/epigenomes8040041 - 3 Nov 2024
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by its aggressive progression and dismal prognosis. Advances in epigenetic profiling, specifically DNA methylation analysis, have significantly deepened our understanding of PDAC pathogenesis. This review synthesizes findings from recent genome-wide DNA
[...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by its aggressive progression and dismal prognosis. Advances in epigenetic profiling, specifically DNA methylation analysis, have significantly deepened our understanding of PDAC pathogenesis. This review synthesizes findings from recent genome-wide DNA methylation studies, which have delineated a complex DNA methylation landscape differentiating between normal and cancerous pancreatic tissues, as well as across various stages and molecular subtypes of PDAC. These studies identified specific differentially methylated regions (DMRs) that not only enhance our grasp of the epigenetic drivers of PDAC but also offer potential biomarkers for early diagnosis and prognosis, enabling the customization of therapeutic approaches. The review further explores how DNA methylation profiling could facilitate the development of subtype-tailored therapies, potentially improving treatment outcomes based on precise molecular characterizations. Overall, leveraging DNA methylation alterations as functional biomarkers holds promise for advancing our understanding of disease progression and refining PDAC management strategies, which could lead to improved patient outcomes and a deeper comprehension of the disease’s underlying biological mechanisms.
Full article
(This article belongs to the Special Issue New Insights into Epigenetic Regulation in Cancer)
►
Show Figures
Open AccessArticle
Transcription Factors Are Involved in Wizened Bud Occurrence During the Growing Season in the Pyrus pyrifolia Cultivar ‘Sucui 1’
by
Hui Li, Jialiang Kan, Chunxiao Liu, Qingsong Yang, Jing Lin and Xiaogang Li
Epigenomes 2024, 8(4), 40; https://doi.org/10.3390/epigenomes8040040 - 25 Oct 2024
Abstract
Background: Flowers are important plant organs, and their development is correlated with yield in woody fruit trees. For Pyrus pyrifolia cultivar ‘Sucui 1’, the research on how DNA methylation accurately regulates the expression of TFs and affects the specific regulatory mechanism of flower
[...] Read more.
Background: Flowers are important plant organs, and their development is correlated with yield in woody fruit trees. For Pyrus pyrifolia cultivar ‘Sucui 1’, the research on how DNA methylation accurately regulates the expression of TFs and affects the specific regulatory mechanism of flower bud wizening will help reduce wizened buds. Methods: Here, the DNA methylomes and transcriptomes of two types of flower buds from the Pyrus pyrifolia cultivar ‘Sucui 1’ were compared. Results: 320 differentially expressed transcription factors (TFs), in 43 families, were obtained from the wizened bud transcriptome versus the normal bud transcriptome. Most were members of the AP2/ERF, bHLH, C2H2, CO-like, MADS, MYB, and WRKY families, which are involved in flower development. As a whole, the methylation level of TFs in the ‘Sucui 1’ genome increased once flower bud wizening occurred. A cytosine methylation analysis revealed that the methylation levels of the same gene regions in TFs from two kinds of buds were similar. However, differentially methylated regions were found in gene promoter sequences. The combined whole-genome bisulfite sequencing and RNA-Seq analyses revealed 162 TF genes (including 164 differentially methylated regions) with both differential expression and methylation differences between the two flower bud types. Among them, 126 were classified as mCHH-type methylation genes. Furthermore, the transcriptional down regulation of PpbHLH40, PpERF4, PpERF061, PpLHW, PpMADS6, PpZF-HD11, and PpZFP90 was accompanied by increased DNA methylation. However, PpbHLH130, PpERF011, and PpMYB308 displayed the opposite trend. The expression changes for these TFs were negatively correlated with their methylation states. Conclusions: Overall, our results offer initial experimental evidence of a correlation between DNA methylation and TF transcription in P. pyrifolia in response to bud wizening. This enriched our understanding of epigenetic modulations in woody trees during flower development.
Full article
(This article belongs to the Collection Epigenetic Control in Plants)
►▼
Show Figures
Figure 1
Open AccessArticle
Epigenome Mapping in Quiescent Cells Reveals a Key Role for H3K4me3 in Regulation of RNA Polymerase II Activity
by
Shengyuan Zeng and Karl Ekwall
Epigenomes 2024, 8(4), 39; https://doi.org/10.3390/epigenomes8040039 - 22 Oct 2024
Abstract
(1) Background: Quiescent cells are those that have stopped dividing and show strongly reduced levels of gene expression during dormancy. In response to appropriate signals, the cells can wake up and start growing again. Many histone modifications are regulated in quiescence, but their
[...] Read more.
(1) Background: Quiescent cells are those that have stopped dividing and show strongly reduced levels of gene expression during dormancy. In response to appropriate signals, the cells can wake up and start growing again. Many histone modifications are regulated in quiescence, but their exact functions remain to be determined. (2) Methods: Here, we map the different histone modifications, H3K4me3, H3K9ac, H3K9me2, and H3K9me3, and the histone variant H2A.Z, comparing vegetative and quiescent fission yeast (S. pombe) cells. We also map histone H3 as a control and RNA polymerase II (phosphorylated at S2 and S5) to enable comparisons of their occupancies within genes. We use ChIP-seq methodology and several different bioinformatics tools. (3) Results: The histone modification mapping data show that H3K4me3 changes stand out as being the most significant. Changes in occupancy of histone variant H2A.Z were also significant, consistent with earlier studies. Regarding gene expression changes in quiescence, we found that changes in mRNA levels were associated with changes in occupancy of RNA polymerase II (S2 and S5). Analysis of quiescence genes showed that increased H3K4me3 levels and RNA polymerase II occupancy were super-significant in a small set of core quiescence genes that are continuously upregulated during dormancy. We demonstrate that several of these genes were require Set1C/COMPASS activity for their strong induction during quiescence. (4) Conclusions: Our results imply that regulation of gene expression in quiescent cells involves epigenome changes with a key role for H3K4me3 in regulation of RNA polymerase II activity, and that different gene activation mechanisms control early and core quiescence genes. Thus, our data give further insights into important epigenome changes in quiescence using fission yeast as an experimental model.
Full article
(This article belongs to the Special Issue Histone Variants)
►▼
Show Figures
Figure 1
Open AccessArticle
Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels
by
Andrea Stoccoro, Martina Lari, Lucia Migliore and Fabio Coppedè
Epigenomes 2024, 8(4), 38; https://doi.org/10.3390/epigenomes8040038 - 9 Oct 2024
Abstract
Background/Objectives: One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could
[...] Read more.
Background/Objectives: One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels. Methods: In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects. Results: We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; p = 0.03), while no significant correlation was observed with folate (r = 0.02; p = 0.80) or homocysteine levels (r = 0.02; p = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (p = 0.04). Conclusions: This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.
Full article
(This article belongs to the Special Issue A Commemorative Issue in Honor of the 30th Anniversary of the Epigenetics Society)
►▼
Show Figures
Figure 1
Open AccessArticle
Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
by
Jenny van Dongen, Charles E. Breeze and Twinning Genetics Consortium
Epigenomes 2024, 8(4), 37; https://doi.org/10.3390/epigenomes8040037 - 6 Oct 2024
Abstract
Background/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a robust DNA
[...] Read more.
Background/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a robust DNA methylation signature in somatic tissues from human monozygotic (MZ) twins, comprising 834 differentially methylated positions (MZ-DMPs). The results point to a connection between monozygotic twinning and early genome programming and enable new angles to study monozygotic twinning. Methods: The mammalian methylation array (MMA) measures 38,608 CpGs focusing on regions that are well-conserved across many mammalian species, allowing for pan-mammalian comparative epigenomic studies. Here, we successfully map human MZ-DMPs to probes of the mammalian methylation array across 157 mammalian genomes. Results: As expected, based on the modest probe overlap between Illumina 450k/EPIC and mammalian methylation array probes, only a subset of MZ-DMPs reside in conserved regions covered by the mammalian methylation array. These include probes mapping to NPAS3, KLHL35, CASZ1, and ATP2B2. Re-analysis restricting the original EWAS in humans to conserved MMA regions yielded additional MZ-DMPs, suggesting that more loci may be detected by application of the mammalian array to monozygotic twins. Conclusions: In conclusion, the mammalian methylation array may prove to be a promising platform to study whether a shared DNA methylation signature of sporadic polyembryony exists across diverse mammalian species. This may potentially point to shared underlying mechanisms.
Full article
(This article belongs to the Collection Feature Papers in Epigenomes)
►▼
Show Figures
Figure 1
Open AccessReview
PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers
by
Tingyu Fan, Jianlian Xie, Guo Huang, Lili Li, Xi Zeng and Qian Tao
Epigenomes 2024, 8(3), 36; https://doi.org/10.3390/epigenomes8030036 - 15 Sep 2024
Abstract
Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone
[...] Read more.
Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone lysine demethylase (KDM) playing an important role in epigenetic modification. Characterized by the zinc finger plant homology domain (PHD) and the Jumonji C (JmjC) domain, PHF8 preferentially binds to H3K4me3 and erases repressive methyl marks, including H3K9me1/2, H3K27me1, and H4K20me1. PHF8 is indispensable for developmental processes and the loss of PHF8 enzyme activity is linked to neurodevelopmental disorders. Moreover, increasing evidence shows that PHF8 is highly expressed in multiple tumors as an oncogenic factor. These findings indicate that studying the role of PHF8 will facilitate the development of novel therapeutic agents by the manipulation of PHF8 demethylation activity. Herein, we summarize the current knowledge of PHF8 about its structure and demethylation activity and its involvement in development and human diseases, with an emphasis on nervous system disorders and cancer. This review will update our understanding of PHF8 and promote the clinical transformation of its predictive and therapeutic value.
Full article
(This article belongs to the Special Issue A Commemorative Issue in Honor of the 30th Anniversary of the Epigenetics Society)
►▼
Show Figures
Figure 1
Open AccessReview
Retrotransposons and Diabetes Mellitus
by
Andromachi Katsanou, Charilaos Kostoulas, Evangelos Liberopoulos, Agathocles Tsatsoulis, Ioannis Georgiou and Stelios Tigas
Epigenomes 2024, 8(3), 35; https://doi.org/10.3390/epigenomes8030035 - 6 Sep 2024
Abstract
Retrotransposons are invasive genetic elements, which replicate by copying and pasting themselves throughout the genome in a process called retrotransposition. The most abundant retrotransposons by number in the human genome are Alu and LINE-1 elements, which comprise approximately 40% of the human genome.
[...] Read more.
Retrotransposons are invasive genetic elements, which replicate by copying and pasting themselves throughout the genome in a process called retrotransposition. The most abundant retrotransposons by number in the human genome are Alu and LINE-1 elements, which comprise approximately 40% of the human genome. The ability of retrotransposons to expand and colonize eukaryotic genomes has rendered them evolutionarily successful and is responsible for creating genetic alterations leading to significant impacts on their hosts. Previous research suggested that hypomethylation of Alu and LINE-1 elements is associated with global hypomethylation and genomic instability in several types of cancer and diseases, such as neurodegenerative diseases, obesity, osteoporosis, and diabetes mellitus (DM). With the advancement of sequencing technologies and computational tools, the study of the retrotransposon’s association with physiology and diseases is becoming a hot topic among researchers. Quantifying Alu and LINE-1 methylation is thought to serve as a surrogate measurement of global DNA methylation level. Although Alu and LINE-1 hypomethylation appears to serve as a cellular senescence biomarker promoting genomic instability, there is sparse information available regarding their potential functional and biological significance in DM. This review article summarizes the current knowledge on the involvement of the main epigenetic alterations in the methylation status of Alu and LINE-1 retrotransposons and their potential role as epigenetic markers of global DNA methylation in the pathogenesis of DM.
Full article
(This article belongs to the Collection Epigenetic Mechanisms in Diabetes Research)
►▼
Show Figures
Figure 1
Open AccessReview
Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies
by
Lara Saftić Martinović, Tea Mladenić, Dora Lovrić, Saša Ostojić and Sanja Dević Pavlić
Epigenomes 2024, 8(3), 34; https://doi.org/10.3390/epigenomes8030034 - 5 Sep 2024
Abstract
Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in
[...] Read more.
Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in infertility, with a focus on DNA methylation, histone modification, and non-coding RNAs. We investigate the specific epigenetic events that occur during gametogenesis, with a focus on spermatogenesis and oogenesis as distinct processes. Furthermore, we investigate how environmental factors such as diet, stress, and toxin exposure can influence these epigenetic changes, potentially leading to infertility. The second part of the review explores epigenetic changes as therapeutic targets for infertility. Emerging therapies that modulate epigenetic marks present promising opportunities for fertility restoration, particularly in spermatogenesis. By summarizing current research findings, this review emphasizes the importance of understanding epigenetic contributions to infertility. Our discussion aims to lay the groundwork for future research directions and clinical applications in reproductive health.
Full article
(This article belongs to the Collection Feature Papers in Epigenomes)
Open AccessArticle
α-Crystalline Domains and Intrinsically Disordered Regions Can Work in Parallel to Induce Accumulation of MBD6 at Chromocenters in Arabidopsis thaliana
by
Brandon A. Boone, Cristy P. Mendoza, Noah J. Behrendt and Steven E. Jacobsen
Epigenomes 2024, 8(3), 33; https://doi.org/10.3390/epigenomes8030033 - 28 Aug 2024
Abstract
Proteins are localized and concentrated at cellular and genomic locations for specific and efficient functions. Efforts to understand protein accumulation in eukaryotic organisms have primarily focused on multivalent interactions between intrinsically disordered regions (IDRs) as mediators of protein condensation. We previously showed that
[...] Read more.
Proteins are localized and concentrated at cellular and genomic locations for specific and efficient functions. Efforts to understand protein accumulation in eukaryotic organisms have primarily focused on multivalent interactions between intrinsically disordered regions (IDRs) as mediators of protein condensation. We previously showed that α-crystalline domain (ACD) proteins 15 (ACD15) and 21 (ACD21) were required for multimerization and the accumulation of gene-silencing methyl-CpG-binding domain protein 6 (MBD6) at chromocenters in Arabidopsis thaliana. Here, we demonstrate that ACDs and IDRs can act as parallel mechanisms, facilitating higher-order MBD6 assemblies. Using human IDRs known to be important for protein accumulation, we replicated and enhanced the accumulation of MBD6 at chromocenters. In addition, IDRs fused to MBD6 could substitute for ACD function and partially reconstitute the MBD6 gene-silencing function. However, the accumulation of MBD6 by IDRs still required ACD15 and ACD21 for full effect. These results establish that ACD-mediated protein accumulation is a mechanism that can function similarly to and together with IDR-mediated mechanisms.
Full article
(This article belongs to the Collection Epigenetic Control in Plants)
►▼
Show Figures
Figure 1
Open AccessArticle
Genome-Wide Methylation Profiling of Peripheral T–Cell Lymphomas Identifies TRIP13 as a Critical Driver of Tumor Proliferation and Survival
by
Pawel Nowialis, Julian Tobon, Katarina Lopusna, Jana Opavska, Arshee Badar, Duo Chen, Reem Abdelghany, Gene Pozas, Jacob Fingeret, Emma Noel, Alberto Riva, Hiroshi Fujiwara, Alexander Ishov and Rene Opavsky
Epigenomes 2024, 8(3), 32; https://doi.org/10.3390/epigenomes8030032 - 21 Aug 2024
Abstract
Cytosine methylation contributes to the regulation of gene expression and normal hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases that include DNMT1, DNMT3A, and DNMT3B. Peripheral T–cell lymphomas (PTCLs) represent aggressive mature T–cell malignancies exhibiting a broad spectrum of
[...] Read more.
Cytosine methylation contributes to the regulation of gene expression and normal hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases that include DNMT1, DNMT3A, and DNMT3B. Peripheral T–cell lymphomas (PTCLs) represent aggressive mature T–cell malignancies exhibiting a broad spectrum of clinical features with poor prognosis and inadequately understood molecular pathobiology. To better understand the molecular landscape and identify candidate genes involved in disease maintenance, we profiled DNA methylation and gene expression of PTCLs. We found that the methylation patterns in PTCLs are deregulated and heterogeneous but share 767 hypo- and 567 hypermethylated differentially methylated regions (DMRs) along with 231 genes up- and 91 genes downregulated in all samples, suggesting a potential association with tumor development. We further identified 39 hypomethylated promoters associated with increased gene expression in the majority of PTCLs. This putative oncogenic signature included the TRIP13 (thyroid hormone receptor interactor 13) gene whose genetic and pharmacologic inactivation inhibited the proliferation of T–cell lines by inducing G2-M arrest and apoptosis. Our data thus show that human PTCLs have a significant number of recurrent methylation alterations that may affect the expression of genes critical for proliferation whose targeting might be beneficial in anti-lymphoma treatments.
Full article
(This article belongs to the Special Issue New Insights into Epigenetic Regulation in Cancer)
►▼
Show Figures
Figure 1
Open AccessArticle
Sex-Specific Associations between Prenatal Exposure to Bisphenols and Phthalates and Infant Epigenetic Age Acceleration
by
Gillian England-Mason, Sarah M. Merrill, Jiaying Liu, Jonathan W. Martin, Amy M. MacDonald, David W. Kinniburgh, Nicole Gladish, Julia L. MacIsaac, Gerald F. Giesbrecht, Nicole Letourneau, Michael S. Kobor and Deborah Dewey
Epigenomes 2024, 8(3), 31; https://doi.org/10.3390/epigenomes8030031 - 10 Aug 2024
Abstract
We examined whether prenatal exposure to two classes of endocrine-disrupting chemicals (EDCs) was associated with infant epigenetic age acceleration (EAA), a DNA methylation biomarker of aging. Participants included 224 maternal–infant pairs from a Canadian pregnancy cohort study. Two bisphenols and 12 phthalate metabolites
[...] Read more.
We examined whether prenatal exposure to two classes of endocrine-disrupting chemicals (EDCs) was associated with infant epigenetic age acceleration (EAA), a DNA methylation biomarker of aging. Participants included 224 maternal–infant pairs from a Canadian pregnancy cohort study. Two bisphenols and 12 phthalate metabolites were measured in maternal second trimester urines. Buccal epithelial cell cheek swabs were collected from 3 month old infants and DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The Pediatric-Buccal-Epigenetic tool was used to estimate EAA. Sex-stratified robust regressions examined individual chemical associations with EAA, and Bayesian kernel machine regression (BKMR) examined chemical mixture effects. Adjusted robust models showed that in female infants, prenatal exposure to total bisphenol A (BPA) was positively associated with EAA (B = 0.72, 95% CI: 0.21, 1.24), and multiple phthalate metabolites were inversely associated with EAA (Bs from −0.36 to −0.66, 95% CIs from −1.28 to −0.02). BKMR showed that prenatal BPA was the most important chemical in the mixture and was positively associated with EAA in both sexes. No overall chemical mixture effects or male-specific associations were noted. These findings indicate that prenatal EDC exposures are associated with sex-specific deviations in biological aging, which may have lasting implications for child health and development.
Full article
(This article belongs to the Collection Feature Papers in Epigenomes)
Open AccessReview
Unravelling the Epigenetic Code: DNA Methylation in Plants and Its Role in Stress Response
by
Emanuela Talarico, Alice Zambelli, Fabrizio Araniti, Eleonora Greco, Adriana Chiappetta and Leonardo Bruno
Epigenomes 2024, 8(3), 30; https://doi.org/10.3390/epigenomes8030030 - 8 Aug 2024
Abstract
Environmental stress significantly affects plant growth, development, and survival. Plants respond to stressors such as temperature fluctuations, water scarcity, nutrient deficiencies, and pathogen attacks through intricate molecular and physiological adaptations. Epigenetic mechanisms are crucial in regulating gene expression in response to environmental stress.
[...] Read more.
Environmental stress significantly affects plant growth, development, and survival. Plants respond to stressors such as temperature fluctuations, water scarcity, nutrient deficiencies, and pathogen attacks through intricate molecular and physiological adaptations. Epigenetic mechanisms are crucial in regulating gene expression in response to environmental stress. This review explores the current understanding of epigenetic modifications, including DNA methylation, and their roles in modulating gene expression patterns under environmental stress conditions. The dynamic nature of epigenetic modifications, their crosstalk with stress-responsive pathways, and their potential implications for plant adaptation and crop improvement are highlighted in the face of changing environmental conditions.
Full article
(This article belongs to the Special Issue Plant Epigenome and Epitranscriptome Adaptation to Environmental Changes)
►▼
Show Figures
Figure 1
Open AccessArticle
Multiomics Screening Identified CpG Sites and Genes That Mediate the Impact of Exposure to Environmental Chemicals on Cardiometabolic Traits
by
Majid Nikpay
Epigenomes 2024, 8(3), 29; https://doi.org/10.3390/epigenomes8030029 - 29 Jul 2024
Abstract
►▼
Show Figures
An understanding of the molecular mechanism whereby an environmental chemical causes a disease is important for the purposes of future applications. In this study, a multiomics workflow was designed to combine several publicly available datasets in order to identify CpG sites and genes
[...] Read more.
An understanding of the molecular mechanism whereby an environmental chemical causes a disease is important for the purposes of future applications. In this study, a multiomics workflow was designed to combine several publicly available datasets in order to identify CpG sites and genes that mediate the impact of exposure to environmental chemicals on cardiometabolic traits. Organophosphate and prenatal lead exposure were previously reported to change methylation level at the cg23627948 site. The outcome of the analyses conducted in this study revealed that, as the cg23627948 site becomes methylated, the expression of the GNA12 gene decreases, which leads to a higher body fat percentage. Prenatal perfluorooctane sulfonate exposure was reported to increase the methylation level at the cg21153102 site. Findings of this study revealed that higher methylation at this site contributes to higher diastolic blood pressure by changing the expression of CHP1 and GCHFR genes. Moreover, HKR1 mediates the impact of B12 supplementation → cg05280698 hypermethylation on higher kidney function, while CTDNEP1 mediates the impact of air pollution → cg03186999 hypomethylation on higher systolic blood pressure. This study investigates CpG sites and genes that mediate the impact of environmental chemicals on cardiometabolic traits. Furthermore, the multiomics approach described in this study provides a convenient workflow with which to investigate the impact of an environmental factor on the body’s biomarkers, and, consequently, on health conditions, using publicly available data.
Full article
Figure 1
Open AccessSystematic Review
DNA Methylation as Drug Sensitivity Marker in RCC: A Systematic Review
by
Antonios Koudonas, Georgios Dimitriadis, Anastasios Anastasiadis and Maria Papaioannou
Epigenomes 2024, 8(3), 28; https://doi.org/10.3390/epigenomes8030028 - 15 Jul 2024
Abstract
►▼
Show Figures
Patient response after treatment of renal cell cancer (RCC) with systemic agents, which include various drug categories, is generally poor and unpredictable. In this context, the ideal drug administration includes tools to predict the sensitivity of the disease to therapy. The aim of
[...] Read more.
Patient response after treatment of renal cell cancer (RCC) with systemic agents, which include various drug categories, is generally poor and unpredictable. In this context, the ideal drug administration includes tools to predict the sensitivity of the disease to therapy. The aim of this study was to systematically summarize the reports on the predictive value of the methylation status in the systemic therapy of RCC. Only original articles reporting on the association of promoter methylation with the response of patients or cell lines to systemic agents were included in this review. We applied PRISMA recommendations to the structure and methodology of this systematic review. Our literature search concluded with 31 articles conducted on RCC cell lines and patient tissues. The majority of the studies demonstrated a methylation-dependent response to systemic agents. This correlation suggests that the methylation pattern can be used as a predictive tool in the management of RCC with various classes of systemic agents. However, although methylation biomarkers show promise for predicting response, the evidence of such correlation is still weak. More studies on the gene methylation pattern in patients under systemic therapy and its correlation with different degrees of response are needed.
Full article
Figure 1
Open AccessReview
Irradiation and Alterations in Hippocampal DNA Methylation
by
Soren Impey and Jacob Raber
Epigenomes 2024, 8(3), 27; https://doi.org/10.3390/epigenomes8030027 - 5 Jul 2024
Abstract
The response of the brain to radiation is important for cancer patients receiving whole or partial brain irradiation or total body irradiation, those exposed to irradiation as part of a nuclear accident or a nuclear war or terrorism event, and for astronauts during
[...] Read more.
The response of the brain to radiation is important for cancer patients receiving whole or partial brain irradiation or total body irradiation, those exposed to irradiation as part of a nuclear accident or a nuclear war or terrorism event, and for astronauts during and following space missions. The mechanisms mediating the effects of irradiation on the hippocampus might be associated with alterations in hippocampal DNA methylation. Changes in cytosine methylation involving the addition of a methyl group to cytosine (5 mC) and especially those involving the addition of a hydroxy group to 5 mC (hydroxymethylcytosine or 5 hmC) play a key role in regulating the expression of genes required for hippocampal function. In this review article, we will discuss the effects of radiation on hippocampal DNA methylation and whether these effects are associated with hippocampus-dependent cognitive measures and molecular measures in the hippocampus involved in cognitive measures. We will also discuss whether the radiation-induced changes in hippocampal DNA methylation show an overlap across different doses of heavy ion irradiation and across irradiation with different ions. We will also discuss whether the DNA methylation changes show a tissue-dependent response.
Full article
(This article belongs to the Collection Feature Papers in Epigenomes)
►▼
Show Figures
Figure 1
Open AccessReview
Oncogenic Roles of UHRF1 in Cancer
by
Ahhyun Kim and Claudia A. Benavente
Epigenomes 2024, 8(3), 26; https://doi.org/10.3390/epigenomes8030026 - 1 Jul 2024
Abstract
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an essential protein involved in the maintenance of repressive epigenetic marks, ensuring epigenetic stability and fidelity. As an epigenetic regulator, UHRF1 comprises several functional domains (UBL, TTD, PHD, SRA, RING) that are collectively
[...] Read more.
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an essential protein involved in the maintenance of repressive epigenetic marks, ensuring epigenetic stability and fidelity. As an epigenetic regulator, UHRF1 comprises several functional domains (UBL, TTD, PHD, SRA, RING) that are collectively responsible for processes like DNA methylation, histone modification, and DNA repair. UHRF1 is a downstream effector of the RB/E2F pathway, which is nearly universally deregulated in cancer. Under physiological conditions, UHRF1 protein levels are cell cycle-dependent and are post-translationally regulated by proteasomal degradation. Conversely, UHRF1 is overexpressed and serves as an oncogenic driver in multiple cancers. This review focuses on the functional domains of UHRF1, highlighting its key interacting proteins and oncogenic roles in solid tumors including retinoblastoma, osteosarcoma, lung cancer, and breast cancer. Additionally, current therapeutic strategies targeting UHRF1 domains or its interactors are explored, providing an insight on potential clinical applications.
Full article
(This article belongs to the Special Issue New Insights into Epigenetic Regulation in Cancer)
►▼
Show Figures
Figure 1
Open AccessReview
Epigenetic Regulation of Mammalian Cardiomyocyte Development
by
Isaiah K. Mensah and Humaira Gowher
Epigenomes 2024, 8(3), 25; https://doi.org/10.3390/epigenomes8030025 - 29 Jun 2024
Abstract
The heart is the first organ formed during mammalian development and functions to distribute nutrients and oxygen to other parts of the developing embryo. Cardiomyocytes are the major cell types of the heart and provide both structural support and contractile function to the
[...] Read more.
The heart is the first organ formed during mammalian development and functions to distribute nutrients and oxygen to other parts of the developing embryo. Cardiomyocytes are the major cell types of the heart and provide both structural support and contractile function to the heart. The successful differentiation of cardiomyocytes during early development is under tight regulation by physical and molecular factors. We have reviewed current studies on epigenetic factors critical for cardiomyocyte differentiation, including DNA methylation, histone modifications, chromatin remodelers, and noncoding RNAs. This review also provides comprehensive details on structural and morphological changes associated with the differentiation of fetal and postnatal cardiomyocytes and highlights their differences. A holistic understanding of all aspects of cardiomyocyte development is critical for the successful in vitro differentiation of cardiomyocytes for therapeutic purposes.
Full article
(This article belongs to the Special Issue A Commemorative Issue in Honor of the 30th Anniversary of the Epigenetics Society)
►▼
Show Figures
Figure 1
Open AccessArticle
DNA Hypomethylation Underlies Epigenetic Swapping between AGO1 and AGO1-V2 Isoforms in Tumors
by
Jean S. Fain, Camille Wangermez, Axelle Loriot, Claudia Denoue and Charles De Smet
Epigenomes 2024, 8(3), 24; https://doi.org/10.3390/epigenomes8030024 - 22 Jun 2024
Abstract
Human tumors progress in part by accumulating epigenetic alterations, which include gains and losses of DNA methylation in different parts of the cancer cell genome. Recent work has revealed a link between these two opposite alterations by showing that DNA hypomethylation in tumors
[...] Read more.
Human tumors progress in part by accumulating epigenetic alterations, which include gains and losses of DNA methylation in different parts of the cancer cell genome. Recent work has revealed a link between these two opposite alterations by showing that DNA hypomethylation in tumors can induce the expression of transcripts that overlap downstream gene promoters and thereby induce their hypermethylation. Preliminary in silico evidence prompted us to investigate if this mechanism applies to the locus harboring AGO1, a gene that plays a central role in miRNA biogenesis and RNA interference. Inspection of public RNA-Seq datasets and RT-qPCR experiments show that an alternative transcript starting 13.4 kb upstream of AGO1 (AGO1-V2) is expressed specifically in testicular germ cells, and becomes aberrantly activated in different types of tumors, particularly in tumors of the esophagus, stomach, and lung. This expression pattern classifies AGO1-V2 into the group of “Cancer-Germline” (CG) genes. Analysis of transcriptomic and methylomic datasets provided evidence that transcriptional activation of AGO1-V2 depends on DNA demethylation of its promoter region. Western blot experiments revealed that AGO1-V2 encodes a shortened isoform of AGO1, corresponding to a truncation of 75 aa in the N-terminal domain, and which we therefore referred to as “∆NAGO1”. Interestingly, significant correlations between hypomethylation/activation of AGO1-V2 and hypermethylation/repression of AGO1 were observed upon examination of tumor cell lines and tissue datasets. Overall, our study reveals the existence of a process of interdependent epigenetic alterations in the AGO1 locus, which promotes swapping between two AGO1 protein-coding mRNA isoforms in tumors.
Full article
(This article belongs to the Special Issue New Insights into Epigenetic Regulation in Cancer)
►▼
Show Figures
Figure 1
Open AccessOpinion
Keep Fingers on the CpG Islands
by
Xing Zhang, Robert M. Blumenthal and Xiaodong Cheng
Epigenomes 2024, 8(2), 23; https://doi.org/10.3390/epigenomes8020023 - 19 Jun 2024
Abstract
The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The
[...] Read more.
The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse Pcsk9 gene, crucial for cholesterol regulation and expressed in hepatocytes, which identified synthetic zinc-finger (ZF) proteins as the most effective DNA-binding editors for silencing Pcsk9 efficiently, specifically, and persistently. This discussion focuses on enhancing the specificity of ZF-array DNA binding by optimizing interactions between specific amino acids and DNA bases across three promoters containing CpG islands.
Full article
(This article belongs to the Special Issue A Commemorative Issue in Honor of the 30th Anniversary of the Epigenetics Society)
►▼
Show Figures
Figure 1
Open AccessReview
Epigenetic Regulation of Neural Stem Cells in Developmental and Adult Stages
by
Shu Kunoh, Hideyuki Nakashima and Kinichi Nakashima
Epigenomes 2024, 8(2), 22; https://doi.org/10.3390/epigenomes8020022 - 4 Jun 2024
Abstract
The development of the nervous system is regulated by numerous intracellular molecules and cellular signals that interact temporally and spatially with the extracellular microenvironment. The three major cell types in the brain, i.e., neurons and two types of glial cells (astrocytes and oligodendrocytes),
[...] Read more.
The development of the nervous system is regulated by numerous intracellular molecules and cellular signals that interact temporally and spatially with the extracellular microenvironment. The three major cell types in the brain, i.e., neurons and two types of glial cells (astrocytes and oligodendrocytes), are generated from common multipotent neural stem cells (NSCs) throughout life. However, NSCs do not have this multipotentiality from the beginning. During cortical development, NSCs sequentially obtain abilities to differentiate into neurons and glial cells in response to combinations of spatiotemporally modulated cell-intrinsic epigenetic alterations and extrinsic factors. After the completion of brain development, a limited population of NSCs remains in the adult brain and continues to produce neurons (adult neurogenesis), thus contributing to learning and memory. Many biological aspects of brain development and adult neurogenesis are regulated by epigenetic changes via behavioral control of NSCs. Epigenetic dysregulation has also been implicated in the pathogenesis of various brain diseases. Here, we present recent advances in the epigenetic regulation of NSC behavior and its dysregulation in brain disorders.
Full article
(This article belongs to the Special Issue Epigenetics of Neurobiology and Brain Diseases)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- Epigenomes Home
- Aims & Scope
- Editorial Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Topical Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Brain Sciences, CIMB, Epigenomes, Genes, IJMS
Genetics and Epigenetics of Substance Use Disorders
Topic Editors: Aleksandra Suchanecka, Anna Maria Grzywacz, Kszysztof ChmielowiecDeadline: 15 November 2025
Conferences
Special Issues
Special Issue in
Epigenomes
A Commemorative Issue in Honor of the 30th Anniversary of the Epigenetics Society
Guest Editors: Humaira Gowher, Assam El-Osta, Andrea FusoDeadline: 31 December 2024
Special Issue in
Epigenomes
The Interplay Between Epigenetics and Inflammation in Chronic Diseases
Guest Editor: Baihai JiaoDeadline: 31 January 2025
Special Issue in
Epigenomes
Longitudinal Studies on Prenatal or Early Life Exposures, Their Associated Epigenetics, and Population Health
Guest Editors: Hongmei Zhang, Yu (Joyce) JiangDeadline: 28 February 2025
Special Issue in
Epigenomes
Epigenetic Mechanisms of Hematologic Malignancies
Guest Editor: Richard L. BennettDeadline: 31 March 2025
Topical Collections
Topical Collection in
Epigenomes
Epigenetic Mechanisms in Diabetes Research
Collection Editor: Assam El-Osta
Topical Collection in
Epigenomes
Epigenetic Regulation of Cellular Differentiation
Collection Editor: Wiesława Leśniak
Topical Collection in
Epigenomes
Feature Papers in Epigenomes
Collection Editors: Ivana De la Serna, Che-Kun James Shen