DNA methylation enables recurrent endogenization of giant viruses in an animal relative

Science Advances, Год журнала: 2024, Номер 10(28)

Опубликована: Июль 12, 2024

5-Methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. In eukaryotes, 5mC has gained complex roles in gene regulation beyond parasite control, yet also been lost many lineages. The causes for retention and its consequences are still poorly understood. Here, we show the protist closely related to animals Amoebidium appalachense features both transposon body methylation, pattern reminiscent of invertebrates plants. Unexpectedly, hypermethylated regions derive from viral insertions, including hundreds endogenized giant viruses, contributing 14% proteome. Using combination inhibitors assays, demonstrate silences these virus insertions. Moreover, alternative isolates polymorphic highlighting dynamic process infection, endogenization, purging. Our results indicate critical controlled coexistence newly acquired DNA into eukaryotic genomes, making unique model understand hybrid origins DNA.

Язык: Английский

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CDH1 (E-cadherin) Gene Methylation in Human Breast Cancer: Critical Appraisal of a Long and Twisted Story

Cancers, Год журнала: 2022, Номер 14(18), С. 4377 - 4377

Опубликована: Сен. 8, 2022

Epigenetic inactivation of a tumor suppressor gene by aberrant DNA methylation is well-established defect in human cells, complementing genetic mutation (germline or somatic). In breast cancer, has diagnostic, prognostic, and predictive potential. A prominent example the hypermethylation CDH1 gene, encoding adhesion protein E-Cadherin (“epithelial cadherin”). numerous publications, it reported as frequently affected cancer. However, over more than two decades research, contradictory results concerning cancer accumulated. Therefore, we review available evidence for against role discuss detail methodological reasons conflicting results, which are general importance analysis specimens. Since loss E-cadherin expression hallmark invasive lobular (ILBC), special attention paid to potential mechanism this subtype Proper understanding basis utmost correct interpretation supposed demonstrate presence clinical relevance

Язык: Английский

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Extensive DNA methylome rearrangement during early lamprey embryogenesis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 4, 2024

Abstract DNA methylation (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, teleosts, for example, exhibit localized maternal-to-paternal remodeling. Here, we studied during embryonic development sea lamprey, jawless occupies critical phylogenetic position as sister group jawed vertebrates. We employed quantification lamprey embryos and tissues, discovered large-scale epigenome remodeling that affects ~30% genome predominantly associated with partially methylated domains. further demonstrate sequences eliminated programmed rearrangement (PGR), hypermethylated sperm prior to onset PGR. Our study thus unveils important insights into evolutionary origins reprogramming, how this process might participate diverse strategies.

Язык: Английский

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Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges

Cancers, Год журнала: 2024, Номер 16(12), С. 2164 - 2164

Опубликована: Июнь 7, 2024

Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer defined by absence of hormone receptor growth factor ERBB2/HER2 expression. It characterized more aggressive course disease shortage effective therapeutic approaches. Hallmarks cells are not only genetic alterations, but also epigenetic aberrations. The studied best understood alterations methylation DNA base cytosine covalent modification histone proteins. reversibility these modifications make them attractive targets for intervention, as documented numerous ongoing clinical trials. Epidrugs, targeting modifications, might offer new options treating triple-negative cancer. Currently, promising combination therapies which epidrug increases efficiency immuncheckpoint inhibitors. This review focusses exclusively on modifications. In reviewing knowledge about especially focus explaining concepts raising awareness what yet known has to be clarified future.

Язык: Английский

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Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria

Genome biology, Год журнала: 2024, Номер 25(1)

Опубликована: Авг. 1, 2024

Abstract Background DNA methylation in the form of 5-methylcytosine (5mC) is most abundant base modification animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, invertebrates, concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, some species, transposable elements (TEs), a pattern known as “mosaic”. Yet, role developmental dynamics how these explain interspecies differences patterns remain poorly understood, especially Spiralia, large clade invertebrates comprising nearly half animal phyla. Results Here, we generate base-resolution methylomes for three species with distinct genomic features phylogenetic positions Annelida, major spiralian phylum. All possible occur annelids, from typical invertebrate intermediate mosaic distribution to hypermethylation loss. GbM common annelids 5mC, explained by taxon-specific transcriptional or presence intronic TEs. Notably, link between transcription decays during development, alongside gradual global, age-dependent demethylation adult stages. Additionally, reducing cytidine analogs early development impairs normal embryogenesis reactivates TEs annelid Owenia fusiformis . Conclusions Our study indicates that global epigenetic erosion aging an ancestral feature bilateral tight gene likely more important embryonic stages, 5mC-mediated TE silencing probably emerged convergently lineages.

Язык: Английский

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Epigenetics Research in Evolutionary Biology: Perspectives on Timescales and Mechanisms

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(9)

Опубликована: Сен. 1, 2024

Epigenetics research in evolutionary biology encompasses a variety of areas, from regulation gene expression to inheritance environmentally mediated phenotypes. Such divergent foci can occasionally render the umbrella term "epigenetics" ambiguous. Here I discuss several areas contemporary epigenetics context biology, aiming provide balanced views across timescales and molecular mechanisms. The importance development is now being assessed many nonmodel species. These studies not only confirm epigenetic marks developmental processes, but also highlight significant diversity regulatory mechanisms taxa. Further, these comparative epigenomic have begun show promise toward enhancing our understanding how programs evolve. A key property that they be inherited along mitotic cell lineages, differences occur during early lasting consequences on organismal Thus, may play roles short-term (within an organism's lifetime or next generation) adaptation phenotypic plasticity. However, extent which observed variation occurs independently genetic influences remains uncertain, due widespread impact genetics limited availability comprehensive (epi)genomic resources most While sequences some species, there little evidence such "transgenerational inheritance" general phenomenon. Rather, are highly variable between

Язык: Английский

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Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review

Frontiers in Genetics, Год журнала: 2024, Номер 15

Опубликована: Июль 2, 2024

Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in healing and regeneration. They are regarded as such due to their capacity self-renewal, multiple differentiation, ability modulate the immune response. However, changes molecular pathways transcription factors of MSCs osteogenesis can lead defects metabolic diseases. DNA methylation is an epigenetic process that plays important role osteogenic differentiation by regulating gene expression. An increasing number studies demonstrated significance methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), signaling about MSCs. This review focuses on progress research these areas.

Язык: Английский

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The evolutionary consequences of interactions between the epigenome, the genome and the environment

Evolutionary Applications, Год журнала: 2024, Номер 17(7)

Опубликована: Июль 1, 2024

Abstract The epigenome is the suite of interacting chemical marks and molecules that helps to shape patterns development, phenotypic plasticity gene regulation, in part due its responsiveness environmental stimuli. There increasing interest understanding functional evolutionary importance this sensitivity under ecologically realistic conditions. Observations epigenetic variation abounds natural populations have prompted speculation it may facilitate responses rapid perturbations, such as those occurring climate change. A frequent point contention whether variants reflect genetic or are independent it. genome often appear tightly linked interdependent. While many changes genetically determined, converse also true, with DNA sequence influenced by presence marks. Understanding how epigenome, environment interact one another therefore an essential step explaining broader consequences epigenomic variation. Drawing on results from experimental comparative studies carried out diverse plant animal species, we synthesize our current these factors populations, a focus identifying similarities differences between taxonomic groups. We describe main components they vary within taxa. review interacts features determinants, role transposable elements (TEs) integrating environment. And look at recent investigating interactions. Although differentiation nature likely result drift selection stochastic epimutations, there growing evidence significant fraction can be stably inherited could contribute evolution independently

Язык: Английский

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Environmental stress during larval development induces DNA methylation shifts in the migratory painted lady butterfly (Vanessa cardui)

Molecular Ecology, Год журнала: 2023, Номер 32(13), С. 3513 - 3523

Опубликована: Апрель 23, 2023

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 unsuitable conditions by migrating. Despite a growing understanding of migration in the life cycles butterfly species, it remains 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‐monotonic 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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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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