Editor’s Highlights from Epigenomics – Spring 2022
Welcome to the first installment of Editor’s Highlights for Epigenomics, which focuses on rapidly progressing research in DNA methylation, array and computational technologies, epigenetic mechanisms and the environmental factors affecting these, among other topics.
In this installment, Storm Johnson, Commissioning Editor of the journal, shares some of their exclusive highlights from the recent journal issues, including an open-access Research Article on experimental biases and quality control tools for the tandem bisulfite and oxidative bisulfite Illumina microarrays.
Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis
First up, I have picked this Preliminary Communication featured in the January issue, led by Editorial Board member Clarisse Musanabaganwa in an international team of researchers from the University of Rwanda (Kigali, Rwanda), the University of South Florida (USA), the Radboud University Medical Center – Donders Institute for Brain, Cognition & Behavior (Heyendaalseweg, The Netherlands), London School of Hygiene & Tropical Medicine (UK), and Uganda Medical Informatics Centre (Entebbe, Uganda). The group conducted a pilot epigenome-wide association study of Tutsi women exposed to the 1994 Rwandan genocide against ethnic Tutsi while pregnant and their resulting offspring. In the past, the genocide has been linked with adverse mental health outcomes in survivors many years later, including post-traumatic stress disorder, depression, anxiety, coronary heart disease and diabetes, among many others.
However, the causal mechanisms contributing to these effects remain a mystery. Epigenetic mechanisms such as DNA methylation are processes cells use to control gene expression and regulate gene function – this may be in response to the embryonic environment controlling which cells will differentiate to become a red blood cell or a hepatocyte. Similarly, these epigenetic processes continue to regulate gene expression over the course of a lifetime in response to environmental exposures and life experiences. In this study, the team identified three differentially methylated regions (DMRs) of the genome in mothers exposed to the genocide; the in-utero exposure was also demonstrated to induce higher methylation levels of these DMRs in the offspring.
Two out of the three DMRs were correlated with brain and blood methylation, suggesting that the peripherally derived signals from the genocide exposure may be relevant to the brain, the authors say. Overall, the results highlight a plausible link between genocide exposure and subsequent poor mental health, both within and between generations.
Check out our Special Focus Issue on Epigenomics and Health Disparities for more articles on this topic.
Atiya Henry, commissioning editor for Future Virology takes us through her highlights of the latest issue of the journal.
Next, I’d like to highlight a Meta-Analysis study conducted by researchers from the Beckman Research Institute of City of Hope (CA, USA), the Shahid Beheshti University of Medical Sciences (Tehran, Iran), and the Babol University of Medical Sciences (Babol, Iran), published in our second January issue. The analysis focuses on a class of short non-coding RNAs known as microRNAs (miRNA, or miR for short), which are translational regulators that bind to messenger RNAs of their target genes to either suppress or degrade them, thereby preventing translation of genes into proteins.
The team home in on miR-31 – one of the most-studied miRNAs whose expression is known to undergo significant changes in colorectal cancer (CRC) – to investigate whether miR-31 is a useful molecular marker in predicting clinical outcomes of CRC. Following a systematic search, they found 16 studies to extract and analyze data on miR-31.
The results demonstrated that there was a correlation between increased levels of miR-31 in the primary tumors of CRC patients and a shorter survival time. High levels of miR-31 were also linked with increased chance of having a mutation in the BRAF gene, which is important in the pathogenesis of CRC, as well as treatment responses. The authors conclude that the molecular marker has predictive value for patient response to frontline treatments for CRC, helping to identify responder and non-responder patients and ultimately plan the course of therapy to ensure survival.
If you want to find out more on this topic, take a look at my interview with the senior author of this paper and Editorial Advisor for the journal, Ajay Goel (Beckman Research Institute of City of Hope).
Navigating the hydroxymethylome: experimental biases and quality control tools for the tandem bisulfite and oxidative bisulfite Illumina microarrays
In this Research Article featured in our February issue, Editorial Advisor and senior author Lucas Salas (Dartmouth College, USA) collaborates with co-authors from Dartmouth College and Brown University School of Public Health (USA) to assess the experimental biases and importance of quality control in two important epigenomic microarray technologies.
The team focussed on techniques that measure DNA hydroxymethylation (5-hydroxymethylcytosine [5hmC]), which is a chemical modification of the DNA that affects gene transcription and has gained traction as a biomarker for early cancer detection and survival prediction in recent years. The authors identify a consistent loss of high-quality data in oxidative bisulfite-treated samples compared with tandem bisulfite-treated samples and offer a bioinformatic tool to help evaluate potential quality issues when using these techniques. The authors emphasize the importance of preserving DNA integrity when measuring 5hmC, and particularly the need for quality control during oxidative bisulfite conversion to minimize information loss.
Correlation among maternal risk factors, gene methylation and disease severity in females with autism spectrum disorder
Finally, in our recent February issue, we feature a Research Article by senior author and Editorial Board member Fabio Coppede and colleagues from the University of Pisa (Italy) and the Istituto di Ricovero e Cura a Carattere Scientifico Stella Maris Foundation (Pisa, Italy). The study set out to detect early-life environmental factors leading to DNA methylation changes of autism spectrum disorder (ASD)-related genes in young females with ASD and whether these methylation levels could be epigenetic biomarkers of ASD severity.
Early-life maternal factors can leave ‘marks’ on the DNA of the developing fetus in utero, these marks include changes in DNA methylation. Due to changes in gene expression levels caused by altered DNA methylation, some maternal factors such as high gestational weight and maternal folic acid supplementation can impact the risk for offspring developing ASD. By investigating blood methylation levels of ASD-related genes in the children with ASD and associating these results with answers from a questionnaire completed by the mothers of the ASD children, the team discovered a correlation between maternal gestational weight gain and BDNF methylation level: BDNF is an important gene involved in brain development. The researchers also found that lack of folic acid supplementation at periconception resulted in more severe ASD. The authors call for further clarification as to whether early-life environmental factors can lead to sex-specific epigenetic differences in ASD-related genes and how these differences can contribute to the sex bias in ASD prevalence.
That’s all for my top picks of Epigenomics published in Spring 2022 – stay tuned for the Summer 2022 update in June!
Be sure to get in touch if you have any queries about the journal Epigenomics or are interested in publishing your own work.
Our latest issue can be found here.
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