Transient DNMT1 suppression reveals hidden heritable marks in the genome

McGraw, Serge; Zhang, Jacques X.; Farag, Mena; Chan, Donovan; Caron, Maxime; Konermann, Carolin; Oakes, Christopher C.; Mohan, K. Naga; Plass, Christoph; Pastinen, Tomi; Bourque, Guillaume; Chaillet, J. Richard; Trasler, Jacquetta M.

doi:10.1093/nar/gku1386

Cited by 37 publications

(51 citation statements)

References 52 publications

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“…[43][44][45][46][47] Briefly, 600 ng of genomic DNA was digested over night with non-methylation specific Msp1 enzyme (NEB # R0106M). [43][44][45][46][47] Briefly, 600 ng of genomic DNA was digested over night with non-methylation specific Msp1 enzyme (NEB # R0106M).…”

Section: Reduced Representation Bisulfite Sequencingmentioning

confidence: 99%

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

et al. 2019

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. contributed equally to this study.Abbreviations: ASD, autism spectrum disorder; CpG, cytosine followed by guanine; DMR, differentially methylated region; DOHaD, developmental origins of health and disease; E. coli, Escherichia coli; GO, gene ontology; LPS, lipopolysaccharide; P3, postnatal day 3; P4, postnatal day 4; P24, postnatal day 24; PBS, phosphate-buffered saline; PFA, paraformaldehyde; RRBS, reduced representation bisulfite sequencing; WMI, white matter injury. AbstractPreterm infants are vulnerable to inflammation-induced white matter injury (WMI), which is associated with neurocognitive impairment and increased risk of neuropsychiatric diseases in adulthood. Epigenetic mechanisms, particularly DNA methylation, play a role in normal development and modulate the response to pathological challenges. Our aims were to determine how WMI triggered DNA methylation alterations in brains of neonatal rats and if such changes persisted over time. We used a robust model of WMI by injecting lipopolysaccharide (LPS) or sterile saline in the corpus callosum of 3-day-old (P3) rat pups. Brains were collected 24 hours (P4) and 21 days post-injection (P24). We extracted genomic DNA from the brain to establish genome-wide quantitative DNA methylation profiles using reduced representation bisulfite sequencing. Neonatal LPS exposure induced a persistent increased methylation of genes related to nervous system development and a reduced methylation of genes associated with inflammatory pathways. These findings suggest that early-life neuroinflammatory exposure impacts the cerebral methylation landscape with determining widespread epigenetic modifications especially in genes related to neurodevelopment. K E Y W O R D SDNA methylation, epigenetics, lipopolysaccharide, periventricular leukomalacia

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Section: Reduced Representation Bisulfite Sequencingmentioning

confidence: 99%

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

et al. 2019

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“…Quantitative methylation analysis of specific repeat regions was done using MassArray Epityper technology (Sequenom, San Diego, CA, USA) as previously described (Ehrich et al, 2005;McGraw et al, 2015).…”

Section: Quantitative Methylation Analysis Of Repeat Regionsmentioning

confidence: 99%

“…MCIp experiments were done as previously described (Gebhard et al, 2006;McGraw et al, 2015). Signals with >0.7-fold enrichment were selected for further analysis.…”

Section: Dna Methylation Profiling By Mcip and Array Hybridizationmentioning

confidence: 99%

Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation

et al. 2016

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STUDY QUESTION: Do short-term and long-term exposures to low-dose folic acid supplementation alter DNA methylation in sperm?SUMMARY ANSWER: No alterations in sperm DNA methylation patterns were found following the administration of low-dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared.WHAT IS KNOWN ALREADY: Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate's role in one-carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high-dose (5 mg/day) folic acid supplementation.STUDY DESIGN, SIZE, DURATION: This is a control versus treatment study where genome-wide sperm DNA methylation patterns were examined prior to fortification of food (1996)(1997) in men with no history of infertility at baseline and following 90-day exposure to placebo (n = 9) or supplement containing 400 μg folic acid/day (n = 10). Additionally, pre-fortification sperm DNA methylation profiles (n = 19) were compared with those of a group of post-fortification (post-2004) men (n = 8) who had been exposed for several years to dietary folic acid fortification. PARTICIPANTS/MATERIALS, SETTING, METHODS:Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole-genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array.MAIN RESULTS AND THE ROLE OF CHANCE: Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first-generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre-and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. † These authors contributed equally to the work.

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“…Protective mechanisms that prevent DNA demethylation of specific regions exist, at the same time that DNA methyltransferase DNMT1 and de novo DNA methyltransferases (DNMT3A,B) are expressed in mouse early embryonic development . The process of DNA methylation remodeling is linked directly to the viability of the embryo, as revealed by embryonic lethality after DNMT1 or DNMT3B mouse knockouts, and to the capacity of germinal cells to transmit information to perpetuate the species, as evidenced by the knockout of DNMT3A or the recently discovered DNMT3C in the male germline in mouse .…”

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DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies)

et al. 2017

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DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children.

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Transient DNMT1 suppression reveals hidden heritable marks in the genome

Cited by 37 publications

References 52 publications

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation

DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies)

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