A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure

Carey, Jenny L.; Cox, Olivia; Seifuddin, Fayaz; Marque, Leonard O.; Tamashiro, Kellie L.K.; Zandi, Peter P.; Wand, Gary S.; Lee, Richard S.

doi:10.3791/58617

Cited by 4 publications

(1 citation statement)

References 26 publications

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“…This method allows quantitative analysis of DNA methylation with single base resolution [109,110]. The rat SureSelect MethylSeq has been designed to target non-redundant promoters, CpG islands, island shores as well as previously identified GC-rich sequences [111]. Sixteen samples were selected to undergo SureSelect Methyl-Seq library preparation: sham-irradiated rats at 1.5 months (n = 4), 27.6 Gy irradiated rats at 1.5 months (n = 4), sham-irradiated rats at 7 months (n = 4) and 27.6 Gy irradiated rats at 7 months (n = 4).…”

Section: Gene-specific Dna Methylation Analysis Using Sureselect Meth...mentioning

confidence: 99%

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

Sallam

Mysara

Benotmane

et al. 2022

IJMS

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Radiation-Induced CardioVascular Disease (RICVD) is an important concern in thoracic radiotherapy with complex underlying pathophysiology. Recently, we proposed DNA methylation as a possible mechanism contributing to RICVD. The current study investigates DNA methylation in heart-irradiated rats and radiotherapy-treated breast cancer (BC) patients. Rats received fractionated whole heart X-irradiation (0, 0.92, 6.9 and 27.6 Gy total doses) and blood was collected after 1.5, 3, 7 and 12 months. Global and gene-specific methylation of the samples were evaluated; and gene expression of selected differentially methylated regions (DMRs) was validated in rat and BC patient blood. In rats receiving an absorbed dose of 27.6 Gy, DNA methylation alterations were detected up to 7 months with differential expression of cardiac-relevant DMRs. Of those, SLMAP showed increased expression at 1.5 months, which correlated with hypomethylation. Furthermore, E2F6 inversely correlated with a decreased global longitudinal strain. In BC patients, E2F6 and SLMAP exhibited differential expression directly and 6 months after radiotherapy, respectively. This study describes a systemic radiation fingerprint at the DNA methylation level, elucidating a possible association of DNA methylation to RICVD pathophysiology, to be validated in future mechanistic studies.

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Section: Gene-specific Dna Methylation Analysis Using Sureselect Meth...mentioning

confidence: 99%

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

Sallam

Mysara

Benotmane

et al. 2022

IJMS

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Cross-species Association Between Telomere Length and Glucocorticoid Exposure

Lee¹,

Zandi

Santos

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Chronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to an accelerated aging, while the link between chronic GCs exposure and disease onset is well established, the underpinning mechanisms are not clear. Objective we explored the potential nexus between GCs or stress exposure and telomere length. Design, Setting, and Participants rats exposed to three weeks of chronic stress; an iatrogenic mouse model of Cushing’s syndrome (CS); a mouse neuronal cell line; 33 patients with CS and 75 healthy human people were studied. Results 1.Telomere length is associated with exposure to stress in rats: 54.5% (P=0.036) reduction in telomere length in the stressed animals. Genomic DNA extracted from the dentate gyrus of stressed and unstressed rats showed 43.2% reduction in telomere length (P=0.006). 2. Mice were exposed to corticosterone (CORT), this treatment produced a 61.4% reduction in telomere length in the blood gDNA (P=5.75x 10-5). 3. We observed a 40.8% reduction in the telomere length in patients with active CS compared to healthy controls (P=0.006). There was a 17.8% reduction in telomere length in cured CS patients, no different from controls (P=0.08). For both cured and active CS, telomere length correlated significantly with the duration of hypercortisolism (R2=0.22, P=0.007). 4. There was a 27.6% reduction in telomere length between low vs. high tertiles in bedtime cortisol levels (P=0.019). Conclusions Our findings demonstrate that exposure to stress and/or glucocorticoids is associated with shortened telomeres, and that shortening may be partially reversible.

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DNA methylation dynamic in male rat germ cells during gametogenesis

et al. 2023

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In mammals, a near complete resetting of DNA methylation (DNAme) is observed during germline establishment. This wave of epigenetic reprogramming is sensitive to the environment which could impair the establishment of an optimal state of the gametes’ epigenome, hence proper embryo development. Yet, we lack a comprehensive understanding of DNAme dynamics during spermatogenesis, especially in rats, the model of choice for toxicological studies. Using a combination of cell sorting and DNA methyl-seq capture, we generated a stage-specific mapping of DNAme in 9 populations of differentiating germ cells from perinatal life to spermiogenesis. DNAme was found to reach its lowest level at gestational day 18, the last demethylated coding regions being associated with negative regulation of cell movement. The following de novo DNAme displayed three different kinetics with common and distinct genomic enrichments, suggesting a non-random process. DNAme variations were also detected at key steps of chromatin remodeling during spermiogenesis, revealing potential sensitivity. These methylome datasets for coding sequences during normal spermatogenesis in rat provide an essential reference for studying epigenetic-related effects of disease or environmental factors on the male germline.

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A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure

Cited by 4 publications

References 26 publications

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

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

Cross-species Association Between Telomere Length and Glucocorticoid Exposure

DNA methylation dynamic in male rat germ cells during gametogenesis

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