The third barrier to transgenerational inheritance in animals: somatic epigenetic resetting

EMBO Reports, Год журнала: 2023, Номер 24(4)

Опубликована: Март 2, 2023

After early controversy, it is now increasingly clear that acquired responses to environmental factors may perpetuate across multiple generations-a phenomenon termed transgenerational epigenetic inheritance (TEI). Experiments with Caenorhabditis elegans, which exhibits robust heritable effects, demonstrated small RNAs as key of TEI. Here, we discuss three major barriers TEI in animals, two which, the "Weismann barrier" and germline reprogramming, have been known for decades. These are thought effectively prevent mammals but not same extent C. elegans. We argue a third barrier-that "somatic resetting"-may further inhibit and, unlike other two, restricts elegans well. While information can overcome Weismann barrier transmit from soma germline, usually cannot "travel back" directly subsequent generations. Nevertheless, memory still influence animal's physiology by indirectly modifying gene expression somatic tissues.

Язык: Английский

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Extensive DNA methylome rearrangement during early lamprey embryogenesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 25, 2023

ABSTRACT DNA methylation (5-methylcytosine, 5mC) is a repressive gene regulatory mark widespread in vertebrate genomes, yet the developmental dynamics which 5mC patterns are established vary across species. While mammals undergo two rounds of global erasure, zebrafish genome exhibits localized maternal-to-paternal remodeling, sperm epigenome inherited early embryo. To date, it unclear how evolutionarily conserved such remodeling strategies are, and what their biological function is. Here, we studied during embryonic development sea lamprey ( Petromyzon marinus ), jawless occupies critical phylogenetic position as sister group jawed vertebrates. We employed base-resolution quantification germline, somatic tissues, discovered large-scale that affects >30% predominantly associated with partially methylated domains (PMDs). further demonstrate sequences eliminated programmed rearrangement (PGR), hallmark embryogenesis, hypermethylated prior to onset PGR. Our study thus unveils important insights into evolutionary origins reprogramming, this process might participate diverse strategies.

Язык: Английский

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Evolution and Diversity of DNA Methylation in Eukaryotes

Опубликована: Янв. 1, 2024

Язык: Английский

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Introduction of cytosine-5 DNA methylation sensitizes cells to oxidative damage

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 13, 2024

Abstract DNA methylation at the 5 position of cytosine (5mC) is an ancient epigenetic mark in eukaryotes. The levels total 5mC vary enormously between different species, and methyltransferases that introduce have been repeatedly lost several independent lineages. are a threat to genomic stability due increased mutagenicity bases propensity themselves alkylation damage as off-target effect. However, whether explains why frequently evolution unclear. Here we tested fitness consequences methyltransferase-induced by introducing eukaryotic-like system into E. coli . We showed genome-wide leads sensitivity alkylating agents, which strongly enhanced removal 3mC repair enzyme AlkB. Unexpectedly, discovered introduction led oxidative stress. this formation reactive oxygen presence 5mC. determined species non-enzymatic oxidation 5mC, producing modified cytosines such 5fC recognised base Overall, our work identifies stress, well negative consequence Oxidative stress encountered organisms their environment, thus offering plausible reason for loss some species.

Язык: Английский

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Introduction of cytosine-5 DNA methylation sensitizes cells to oxidative damage

Опубликована: Ноя. 15, 2024

DNA methylation at the 5 position of cytosine (5mC) is an ancient epigenetic mark in eukaryotes. The levels total 5mC vary enormously between different species, and methyltransferases that introduce have been repeatedly lost several independent lineages. are a threat to genomic stability due increased mutagenicity bases propensity themselves alkylation damage as off-target effect. However, whether explains why frequently evolution unclear. Here we tested fitness consequences methyltransferase-induced by introducing eukaryotic-like system into E. coli . We showed genome-wide leads sensitivity alkylating agents, which strongly enhanced removal 3mC repair enzyme AlkB. Unexpectedly, discovered introduction led oxidative stress. this formation reactive oxygen presence 5mC. determined species non-enzymatic oxidation 5mC, producing modified cytosines such 5fC recognised base Overall, our work identifies stress, well negative consequence Oxidative stress encountered organisms their environment, thus offering plausible reason for loss some species.

Язык: Английский

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Computational Protocol for DNA Methylation Profiling in Plants Using Restriction Enzyme-Based Genome Reduction

Methods in molecular biology, Год журнала: 2023, Номер unknown, С. 23 - 36

Опубликована: Янв. 1, 2023

Язык: Английский

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Hipermetylacja promotora genu CDH1 w DNA komórek jako biomarker progresji raka jamy ustnej

Опубликована: Янв. 1, 2023

Malignant neoplasms of the head and neck region are sixth most common tumors in world wide population, with 650 000 new cases diagnosed every year 350 deaths. In this group cancers, is oral squamous cell carcinoma (OSCC), which recognized 90% malignant mouth 38% all cancers. Due to large number newly cases, especially relation high mortality low 5-year survival rate, cancer a serious medical problem significant impact on various aspects public health as well having social economic impact. The latest epidemiological data were presented by National Cancer Registry concerning 2019 year. There 2,168 cancer, including 1,726 men 442 women 1,428 deaths caused there 1,165 263 women. According register, decade 2010–2020, Podkarpackie Province, total 1,044 patients suffered from tumors, 819 225 During period, 753 died 636 117 Despite advances preventive activities development therapeutic tools techniques, percentage rates OSCC has remained unchanged for over 20 years. Bad results prognosis closely related late diagnosis initiation process, often advanced stage disease, tumor infiltration surrounding tissues, metastases regional lymph nodes rarely distant other organs. Long-term treatment still unsatisfactory studies have not improved many these reasons, researchers aimed at finding biomarkers, allowing precise monitoring process starting when patient clinical symptoms. One research methods developing biomarker epigenetics. carcinogenesis occurs result simultaneous genetic epigenetic changes. mechanisms regulation gene expression (from Greek epi – above genome), hereditary but potentially reversible changes encoded genome modifications chromatin components important tumorigenesis without DNA sequence. normal chain methylation process. Epigenetic pattern been observed types considered be essential carcinogenesis. early stages abnormalities necessary tissue neoplasia progression development. Different express characteristic patterns, they also features that used detection allow tracking their some significance assessing prognosis. rapid technological progress human practice biomarkers markers progression. consists attaching methyl fifth carbon cytosine ring, however only 3-4% cytosines undergo Changes first associated changing proper functioning include hypermethylation, hypomethylation blocking imprinting. disorders develop gradually ongoing Hypermethylation CpG islands appears methylated successively increasing malignancy. begins spreads, takes up more areas genome. This probably due aging mediators inflammation oxidative stress cell. CDH1 located long arm chromosome 16, 16q22.1 locus encodes E-cadherin protein (epithelial cadherin). 120 kD transmembrane homodimer composed 882 amino acid residues. Scientific evaluating demonstrated key role during invasion. A level activity or lack motility, resulting tissues. suppressor encoding protein. mechanism weakening completely formation hypermethylation promoter gene. Reduced main cause dysfunction intercellular adhesion, partial complete reduction progeny adherence consequently an increased ability infiltrate tissues create metastases. aim study was evaluate effect cells cells, course, dynamics cancer. retrospective study. treated Clinic Maxillofacial Surgery University Clinical Hospital Rzeszów, Oncology Center histological preparations obtained Department Pathology Rzeszów 58 21 Bioethical Commission resolution No. 14/01/2019, agreed conduct part project: “Molecular autoimmune diseases”. I looked surgical margin after excision, course operated concerned correlation between hipermethylation time onset recurrence, nodes, patients’ survival. conducted context searching answer question whether could surgery. Analysis allowed draw conclusions knowledge can follow-up statistically found incidence primary should frequent examination surgery, whom case found, appropriate started soon possible. Similar observations made regarding 4 months shorter confirmed addition, showed positive abusing alcohol, smokers who smoked tobacco my studies, no statistical operative margin, frequency recurrence cavity, local metastases, occurrence nodes. expanded our molecular basis oncogenesis carcinoma, combining determination regions tested results. Continuing may future contribute clinically useful panel, support become foundation oncological drugs based mechanisms.

Язык: Английский

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Transcription factor-mediated direct cellular reprogramming yields cell-type specific DNA methylation signature

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 21, 2023

Abstract Direct reprogramming is a technique for inducing the conversion of one type somatic cell into another by forced expression defined transcription factors. Cell differentiation generally determined specific gene profiles based on distinct genome-wide epigenetic signatures. Although CpG methylation genomic DNA an essential factor that affects transcriptional state genes, little known about how changes and what roles it plays in direct reprogramming. Here, we performed comparative analyses mouse embryonic fibroblasts (MEFs) cells composing organoids formed intestinal stem (ISCs) or induced ISCs (iISCs) were directly from MEFs to investigate impact dynamics We found was similar between forming ISC iISC organoids, while they differed widely those MEFs. Moreover, regions differentially methylated organoid- organoid-forming did not significantly affect expression. These results demonstrate accuracy safety induction, as show transitions close during iISCs.

Язык: Английский

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Transcription factor-mediated direct cellular reprogramming yields cell-type specific DNA methylation signature

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Дек. 15, 2023

Direct reprogramming, inducing the conversion of one type somatic cell into another by forced expression defined transcription factors, is a technology with anticipated medical applications. However, due to many unresolved aspects induction mechanisms, it essential thoroughly analyze epigenomic state generated cells. Here, we performed comparative genome-wide DNA methylation analyses mouse embryonic fibroblasts (MEFs) and cells composing organoids formed intestinal stem (ISCs) or induced ISCs (iISCs) that were directly from MEFs. We found CpG was similar between forming ISC iISC organoids, while they differed widely those in Moreover, genomic regions differentially methylated organoid- organoid-forming did not significantly affect gene expression. These results demonstrate accuracy safety induction, leading applications this technology.

Язык: Английский

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Environmental stress during larval development induces head methylome profile shifts in the migratory painted lady butterfly (Vanessa cardui)

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Ноя. 14, 2022

Abstract Seasonal environmental fluctuations provide formidable challenges for living organisms, especially small ectotherms such as butterflies. A common strategy to cope with harsh environments is enter diapause, but some species avoid the unsuitable conditions by migrating. Despite a growing understanding of migration in life cycles butterfly species, it unknown how individuals register and store cues determine whether where migrate. Here, we explored competition host plant availability during larval development affect patterns DNA methylation migratory painted lady ( Vanessa cardui ) butterfly. We identify set potentially functional methylome shifts associated differences environment, indicating that involved response different development. By analysing transcriptome same samples used profiling, also uncovered non-linear relationship between gene body expression. Our results starting point interplay expression butterflies general can trigger unique epigenetic marks might be important behavioural decisions adult stage.

Язык: Английский

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