Next Issue
Volume 5, June
Previous Issue
Volume 4, December

Epigenomes, Volume 5, Issue 1 (March 2021) – 6 articles

Cover Story (view full-size image): A human telomere consists of a tract of tandemly repeated short DNA sequences d(TTAGGG) with a single-stranded overhang that can form G-quadruplex (G4) structures. In this study, the effects of N6-methyladenine (m6dA) modification on the thermal stability of four distinct telomeric G4 structures were investigated. Circular dichroism melting analysis demonstrated that the telomeric G4 structures formed in K+ were stabilized by m6dA modifications. Moreover, the thermal stability of the telomeric G4 structure formed in Na+ changed depending on the position of m6dA modification. These results contribute to the understanding of telomere biology, which can lead to applications in anti-cancer drug development. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Order results
Result details
Select all
Export citation of selected articles as:
Article
Ultra-Low DNA Input into Whole Genome Methylation Assays and Detection of Oncogenic Methylation and Copy Number Variants in Circulating Tumour DNA
Epigenomes 2021, 5(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010006 - 19 Feb 2021
Cited by 1 | Viewed by 1165
Abstract
Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) [...] Read more.
Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at the genome-wide level because of lack of available input. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50 ng); eighteen blood derived specimens (lowest input 10 ng) and six matched ctDNA input (lowest input 10 ng)/fresh tumour specimens (lowest input 250 ng) were processed. Downstream analysis was performed in R/Bioconductor for quality control metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation were high at the probe level averaged R2 = 0.99 for blood derived samples and R2 > 0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared, R2 > 0.91 between the two. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample with good concordance via DQ plot. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to an input of 10 ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA. These findings demonstrate that these samples can now be accessed by methylation array technology, allowing analysis of these important sample types. Full article
Show Figures

Figure 1

Article
Thermal Stability Changes in Telomeric G-Quadruplex Structures Due to N6-Methyladenine Modification
Epigenomes 2021, 5(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010005 - 02 Feb 2021
Cited by 1 | Viewed by 1217
Abstract
N6-methyladenine modification (m6dA) has recently been identified in eukaryote genomic DNA. The methylation destabilizes the duplex structure when the adenine forms a Watson–Crick base pair, whereas the methylation on a terminal unpaired adenine stabilizes the duplex structure by increasing [...] Read more.
N6-methyladenine modification (m6dA) has recently been identified in eukaryote genomic DNA. The methylation destabilizes the duplex structure when the adenine forms a Watson–Crick base pair, whereas the methylation on a terminal unpaired adenine stabilizes the duplex structure by increasing the stacking interaction. In this study, the effects of m6dA modification on the thermal stability of four distinct telomeric G-quadruplex (G4) structures were investigated. The m6dA-modified telomeric oligonucleotide d[AGGG(TTAGGG)3] that forms a basket-type G4 in Na+, d[(TTAGGG)4TT] that forms a hybrid-type G4 in K+ (Form-2), d[AAAGGG(TTAGGG)3AA] that forms a hybrid-type G4 in K+ (Form-1), and d[GGG(TTAGGG)3T] that forms a basket-type G4 with two G-tetrads in K+ (Form-3) were analyzed. Circular dichroism melting analysis demonstrated that (1) A7- and A19-methylation destabilized the basket-type G4 structure that formed in Na+, whereas A13-methylation stabilized the structure; (2) A15-methylation stabilized the Form-2 G4 structure; (3) A15- and A21-methylations stabilized the Form-1 G4 structure; and (4) A12-methylation stabilized the Form-3 G4 structure. These results suggest that m6dA modifications may affect the thermal stability of human telomeric G4 structures in regulating the biological functions. Full article
(This article belongs to the Special Issue Recent Advances in Biological Methylation)
Show Figures

Figure 1

Editorial
Acknowledgment to Reviewers of Epigenomes in 2020
Epigenomes 2021, 5(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010004 - 28 Jan 2021
Viewed by 765
Abstract
Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Epigenomes maintains its standards for the high quality of its published papers [...] Full article
Review
Epigenetic Regulators of White Adipocyte Browning
Epigenomes 2021, 5(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010003 - 12 Jan 2021
Cited by 1 | Viewed by 1464
Abstract
Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT [...] Read more.
Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes. Full article
Show Figures

Figure 1

Review
The Role of the PRMT5–SND1 Axis in Hepatocellular Carcinoma
Epigenomes 2021, 5(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010002 - 05 Jan 2021
Viewed by 1288
Abstract
Arginine methylation is an essential post-translational modification (PTM) deposited by protein arginine methyltransferases (PRMTs) and recognized by Tudor domain-containing proteins. Of the nine mammalian PRMTs, PRMT5 is the primary enzyme responsible for the deposition of symmetric arginine methylation marks in cells. The staphylococcal [...] Read more.
Arginine methylation is an essential post-translational modification (PTM) deposited by protein arginine methyltransferases (PRMTs) and recognized by Tudor domain-containing proteins. Of the nine mammalian PRMTs, PRMT5 is the primary enzyme responsible for the deposition of symmetric arginine methylation marks in cells. The staphylococcal nuclease and Tudor domain-containing 1 (SND1) effector protein is a key reader of the marks deposited by PRMT5. Both PRMT5 and SND1 are broadly expressed and their deregulation is reported to be associated with a range of disease phenotypes, including cancer. Hepatocellular carcinoma (HCC) is an example of a cancer type that often displays elevated PRMT5 and SND1 levels, and there is evidence that hyperactivation of this axis is oncogenic. Importantly, this pathway can be tempered with small-molecule inhibitors that target PRMT5, offering a therapeutic node for cancer, such as HCC, that display high PRMT5–SND1 axis activity. Here we summarize the known activities of this writer–reader pair, with a focus on their biological roles in HCC. This will help establish a foundation for treating HCC with PRMT5 inhibitors and also identify potential biomarkers that could predict sensitivity to this type of therapy. Full article
(This article belongs to the Special Issue Recent Advances in Biological Methylation)
Show Figures

Figure 1

Review
Epigenetic Regulation of Epidermal Differentiation
Epigenomes 2021, 5(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5010001 - 01 Jan 2021
Viewed by 1174
Abstract
The epidermis is the outer part of the skin that protects the organism from dehydration and shields from external insults. Epidermal cells, called keratinocytes, undergo a series of morphological and metabolic changes that allow them to establish the biochemical and structural elements of [...] Read more.
The epidermis is the outer part of the skin that protects the organism from dehydration and shields from external insults. Epidermal cells, called keratinocytes, undergo a series of morphological and metabolic changes that allow them to establish the biochemical and structural elements of an effective epidermal barrier. This process, known as epidermal differentiation, is critical for the maintenance of the epidermis under physiological conditions and also under stress or in various skin pathologies. Epidermal differentiation relies on a highly coordinated program of gene expression. Epigenetic mechanisms, which commonly include DNA methylation, covalent histone modifications, and microRNA (miRNA) activity, modulate various stages of gene expression by altering chromatin accessibility and mRNA stability. Their involvement in epidermal differentiation is a matter of intensive studies, and the results obtained thus far show a complex network of epigenetic factors, acting together with transcriptional regulators, to maintain epidermal homeostasis and counteract adverse effects of environmental stressors. Full article
(This article belongs to the Collection Epigenetic Regulation of Cellular Differentiation)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop