Stefanie Seisenberger’s research while affiliated with Babraham Institute and other places

... The TET family comprises three subtypes of methylcytosine dioxygenase, including TET1, TET2, and TET3, each of which is involved in various physiological and pathological processes. The importance of TET1 in the development of embryonic stem cells has been proven [3][4][5], whereas TET2 has been shown to be pivotal in the progression of inflammatory diseases [6,7], atherosclerosis [8,9], diabetes [10], clonal hematopoiesis [8,11], and cancer [10,12]. TET3 has been implicated in promoting the growth of acute myeloid leukemia and the activation of leukemia stem cell-associated pathways [13], as well as in the upregulation of 5-hydroxymethylcytosine (5-hmC) levels in synovitis tissues of rheumatoid arthritis [14]. ...

Reference:

Tet Methylcytosine Dioxygenase 3 Promotes Cardiovascular Senescence by DNA 5‐Hydroxymethylcytosine‐Mediated Sp1 Transcription Factor Expression

... The study however did not include females which means we cannot tell whether different drugs of abuse also show sexually dimorphic transgenerational effects. Human studies have long identified trends of transgenerational epigenetic inheritance which means specific rodent studies are required to identify the underlying mechanisms especially since reports in transgenerational studies on diet have found persistence of behavioural phenotype changes despite the epigenetic markers being wiped out (Bottom et al. 2022;Gapp et al. 2014;Radford et al. 2014). ...

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Preconceptual paternal ethanol drinking induces sexually dimorphic behavioural changes across 2 generations

... Methylation of genes in the male germ line is generally believed to be largely eliminated at fertilization, and stem cells in the early embryo then undergo re-methylation in a cell typespecific way (Lee et al. 2014). However, recent findings from genome-wide DNA methylation studies indicate that some differentially methylated regions are resistant to genome-wide demethylation and de novo re-methylation during embryogenesis and have the potential to affect the next generation (Tang et al. 2015;Radford et al. 2014). On the other hand, we previously conducted genome-wide DNA methylation analyses of F2 embryos by gestational arsenic exposure and reported that the decrease of global DNA methylation levels and the predominance of hypoDMCs observed in F1 sperm were also detected in F2 embryos. ...

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Characteristics of Global Methylation Changes in F1 Mice Sperm DNA Induced by Gestational Arsenic Exposure Are Re‐Established in F2 Somatic Cells but Not in F2 Germ Cells

... DNAm occurs by the addition of a methyl group onto a cytosine-phosphate-guanine base pairing (CpG site), which can decrease/inhibit expression (hypermethylation) or increase expression (hypomethylation) of a gene (Bird, 1986). The prenatal period is a time of particularly high DNAm activity, subsequent methylation of specific CpG sites in specific tissues is critical to embryonic development (Breton-Larrivée et al., 2019;Seisenberger et al., 2013). DNAm occurring in utero also influences gene expression throughout the lifespan (Vaiserman & Lushchak, 2021). ...

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Maternal Smoking During Pregnancy Is Associated With DNA Methylation in Early Adolescence: A Sibling Comparison Design

... Lastly, Siebert (2018) reported results of differential DNAmethylation of Burkitt lymphoma (BL) versus other B-cell lymphomas, including germinal centre B-cell like diffuse large B-cell lymphoma (GCB DLBCL) and FL (Kreck et al, 2013;Kretzmer et al, 2015;Siebert, 2018). Kretzmer et al (2015) demonstrated significant overexpression of mutant SMARCA4 and differentially methylated regions (DMR) in BL versus other B-cell lymphomas. ...

Reference:

Childhood, adolescent and young adult non‐Hodgkin lymphoma: current perspectives

... These erasures facilitate totipotency, while the reestablishment of DNA methylation marks directs cells towards a specific fate. However, studies have shown that the germlines of mice, pigs, and humans exhibit incomplete erasure of DNA methylation (Kearns et al., 2000;Sutherland et al., 2000;Tang et al., 2015;Guo et al., 2017;Gómez-Redondo et al., 2021), with primordial germ cells retaining about 10% of their methylation marks (Seisenberger et al., 2012), while the inner cell mass of the blastocyst retains roughly 20% (L. Wang et al., 2014). ...

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DNA Methylation and its potency in comprehending Multigenerational Influences on Autism Spectrum Disorders in pediatrics

... PFAS can potentially disrupt DNA methylation, histone modification dynamics, and non-coding RNA expression, thereby compromising the precise epigenetic programming required for normal development. Of particular significance are the two waves of epigenetic reprogramming during embryogenesis, which reset and reestablish parent-of-origin methylation patterns critical for imprinting, transposon silencing, and lineage specification [43,47,49,107,108]. Recent advancements in high-resolution and single-cell epigenomic profiling include techniques such as chromatin immunoprecipitation sequencing (ChIP-seq), ATAC-seq, reduced representation bisulfite sequencing (RRBS), and nascent transcript profiling, which have significantly refined our understanding of these processes. ...

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Epigenetic Consequences of In Utero PFAS Exposure: Implications for Development and Long-Term Health

... Sequencing-based methods for methylome analysis can be classified into two groups: bisulfite conversionbased and enrichment-based methods [40]. The former is considered to be the gold standard of DNA methylation analysis [41], however, they are hampered by inefficiencies due to the inability to differentiate between 5mC and 5hmC [42], the degradation of input DNA during conversion, high costs, and limited coverage. ...

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Cancer liquid biopsies by Oxford Nanopore Technologies sequencing of cell-free DNA: from basic research to clinical applications

... В то же время было мало понимания о влиянии деметилирования ДНК до открытия ферментов транслокации Ten-eleven (TET) и их способности к деметилированию путем окисления 5-метилцитозина 5mC до 5-гидроксиметилцитозина (5hmC), а также других производных [43]. Исследования показали, что общий уровень 5hmC в геномной ДНК существенно снижен во многих солидных опухолях, что связано с пониженными уровнями экспрессии членов семейства TET [44,45]. Белки семейства TET способствуют локусспецифическому обратному метилированию ДНК в нормальных клетках, в конечном итоге регулируя экспрессию генов [44]. ...

Reference:

Epigenetic abnormalities and neuroendocrine differentiation in prostate cancer

... DNA methylation usually occurs on CpG islands, mostly in the proximal promoter region of the human genome [7]. DNA methylation alters an individual's biological function by regulating gene expression or genome sequence stability [8]. It can keep transcription factors out of two gene promoters, inhibit transcription factor binding and change chromatin structures. ...

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Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke