DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy

Sallam, Magy; Mysara, Mohamed; Benotmane, Mohammed Abderrafi; Crijns, Anne; Spoor, Daan; Nieuwerburgh, Filip Van; Deforce, Dieter; Baatout, Sarah; Guns, Pieter-Jan; Aerts, An; Ramadan, Raghda

doi:10.3390/ijms232416214

Cited by 5 publications

(1 citation statement)

References 116 publications

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“…DNA methylation also has an important aspect in radiation-induced cardiovascular disease (RICVD), which is an important problem in thoracic radiotherapy with complex pathophysiology. Current studies describe a systemic radiation fingerprint at the level of DNA methylation, explaining the possible relationship of DNA methylation to the pathophysiology of RICVD [ 139 ]. Figure 2 illustrates a cause-and-effect diagram between the drivers of proinflammatory epigenetic changes that contribute to the development of CVDs.…”

Section: Dna Methylation and Its Importance In The Regulation Of The ...mentioning

confidence: 99%

The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target

Wołowiec,

Grześk

et al. 2023

IJMS

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Epigenetics is a rapidly developing science that has gained a lot of interest in recent years due to the correlation between characteristic epigenetic marks and cardiovascular diseases (CVDs). Epigenetic modifications contribute to a change in gene expression while maintaining the DNA sequence. The analysis of these modifications provides a thorough insight into the cardiovascular system from its development to its further functioning. Epigenetics is strongly influenced by environmental factors, including known cardiovascular risk factors such as smoking, obesity, and low physical activity. Similarly, conditions affecting the local microenvironment of cells, such as chronic inflammation, worsen the prognosis in cardiovascular diseases and additionally induce further epigenetic modifications leading to the consolidation of unfavorable cardiovascular changes. A deeper understanding of epigenetics may provide an answer to the continuing strong clinical impact of cardiovascular diseases by improving diagnostic capabilities, personalized medical approaches and the development of targeted therapeutic interventions. The aim of the study was to present selected epigenetic pathways, their significance in cardiovascular diseases, and their potential as a therapeutic target in specific medical conditions.

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Section: Dna Methylation and Its Importance In The Regulation Of The ...mentioning

confidence: 99%

The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target

Wołowiec,

Grześk

et al. 2023

IJMS

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Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome

Cox,

Seifuddin,

Guo

et al. 2024

Epigenetics

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Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat’s immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes. In this study, we implemented the rat Methyl-Seq platform and tested its ability to distinguish differentially methylated regions (DMRs) among three different tissue types, three distinct brain regions, and, in the hippocampus, between males and females. These comparisons yielded DNAm differences of differing magnitudes, many of which were independently validated by bisulfite pyrosequencing, including autosomal regions that were predicted to show the least degree of difference in DNAm between males and females. Quantitative reverse transcription PCR revealed that most genes associated with the DMRs showed tissue-, brain region-, and sex-specific differences in expression. In particular, we found evidence for sex-specific DNAm and expression differences at Tubb6 , Lrrn2 , Tex26 , and Sox5l1 , all of which play important roles in neurodevelopment and have been implicated in studies examining sex differences. Our results demonstrate the utility of the rat Methyl-Seq platform and suggest the presence of DNAm differences between the male and female hippocampus. The rat Methyl-Seq has the potential to provide epigenomic insights into pharmacological and behavioral studies performed in the rat.

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Postsynaptic density radiation signature following space irradiation

et al. 2023

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Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance.Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation.Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density.Discussion: The brain’s response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.

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DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy

Cited by 5 publications

References 116 publications

The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target

The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target

Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome

Postsynaptic density radiation signature following space irradiation

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