Acquired sperm hypomethylation by gestational arsenic exposure is re-established in both the paternal and maternal genomes of post-epigenetic reprogramming embryos

Epigenetics & Chromatin, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 16, 2025

DNA methylation plays a crucial role in mammalian development. While methylome changes acquired the parental genomes are believed to be erased by epigenetic reprogramming, accumulating evidence suggests that sperm caused environmental factors involved disease phenotypes of offspring. These findings imply transferred embryo after reprogramming. However, our understanding this process remains incomplete. Our previous study showed arsenic exposure F0 pregnant mice paternally increased tumor incidence F2 The arsenic-exposed F1 males exhibited characteristic features, including enrichment hypomethylated cytosines at promoters retrotransposons LINEs and LTRs. Hypomethylation is potentially detrimental. Determining whether these hypomethylation important confirming molecular pathway intergenerational transmission paternal effects exposure. We investigated male embryos reprogramming reduced representation bisulfite sequencing (RRBS) allele-specific analysis. To do so, were obtained crossing control or gestationally (C3H/HeN strain) with females (C57BL/6 strain). results revealed group was globally enriched for certain genomic regions, LTR LINE, as observed group. Unexpectedly, features detected not only genome but also maternal embryos. Furthermore, found rarely occur same positions between characteristics arsenic-induced reproduced both post-epigenetic suggest re-establishment achieved collaboration other mediate region-specific changes. highlight possibility could contribute development predisposition

Язык: Английский

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HERV-W Env Induces Neuron Pyroptosis via the NLRP3–CASP1–GSDMD Pathway in Recent-Onset Schizophrenia

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 520 - 520

Опубликована: Янв. 9, 2025

HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, envelope protein gene HERV-W env W family protein), located on chromosome 7 and primarily expressed placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well autoimmune diseases cancer. Recent studies highlighted abnormal expression cytokines a key factor pathophysiology schizophrenia. Notably, elevated serum levels IL-1β (interleukin 1 beta) cytokine associated with inflammation, characteristic feature pyroptosis-a form pro-inflammatory programmed cell death. Although previous research observed significant upregulation pyroptosis-related genes such CASP1 (Caspase-1), NLRP3 (NLR pyrin domain containing 3), IL1B schizophrenia patients, extensive neuron pyroptosis documented Alzheimer's disease, epilepsy, multiple sclerosis, occurrence remains uncertain. Furthermore, mechanisms underlying its potential connection yet be fully elucidated. In this study, we found genes, specifically CASP1, GSDMD (Gasdermin D), IL1B, were significantly patients compared healthy controls. our analysis revealed strong positive correlation between CASP1/GSDMD/IL1B these patients. Experimental evidence further demonstrated promoted activation Caspase-1 cleavage Gasdermin D, leading increased release LDH (lactate dehydrogenase) IL-1β. Importantly, inhibitors targeting NLRP3, reduced releases induced by env, whereas BID (BH3 interacting death agonist) did not notable effect. This suggests induces CASP1-GSDMD-dependent through NLRP3-CASP1-GSDMD signaling pathway. As is increasingly recognized for neurodegenerative diseases, study provides insights molecular neuronal mediated inflammasome context env. Additionally, it explores facilitation development via pyroptosis, proposing certain indicators could serve biomarkers Based existing results findings researchers, infer acts bridge onset progression may target clinical treatment suggesting monoclonal antibody therapy represent novel approach managing disease.

Язык: Английский

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Endogenous retrovirus HERVH-derived lncRNA UCA1 controls human trophoblast development

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(12)

Опубликована: Март 14, 2024

Endogenous retroviruses (ERVs) are frequently reactivated in mammalian placenta. It has been proposed that ERVs contribute to shaping the gene regulatory network of trophoblasts, dominantly acting as species- and placental-specific enhancers. However, whether how control human trophoblast development through alternative pathways remains poorly understood. Besides well-recognized function endogenous retrovirus-H (HERVH) maintaining pluripotency early epiblast, here we present a unique role HERVH on lineage development. We found LTR7C/HERVH subfamily exhibits an accessible chromatin state lineage. Particularly, LTR7C/HERVH-derived

Язык: Английский

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Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

Protein & Cell, Год журнала: 2024, Номер 15(8), С. 612 - 632

Опубликована: Апрель 5, 2024

Abstract Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, worldwide prevalent inflammatory disease. However, systematic characterization comprehensive understanding of regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected phenotypic characteristics during in primates constructed first single-nucleus transcriptomic landscape aging, by which panel cell type-specific signatures were elucidated. Epithelial cells identified as most affected types gingiva. Further analyses pinpointed crucial role YAP epithelial self-renew homeostasis, declined cells, especially basal cells. The decline activity was confirmed human tissues, downregulation primary keratinocytes recapitulated major defects observed aged primate while overexpression showed rejuvenation effects. Our work provides an in-depth serves rich resource for developing novel strategies combat aging-associated diseases, with ultimate goal advancing periodontal health promoting healthy aging.

Язык: Английский

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Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 2, 2024

Язык: Английский

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Genome stability from the perspective of telomere length

Trends in Genetics, Год журнала: 2023, Номер 40(2), С. 175 - 186

Опубликована: Ноя. 11, 2023

Язык: Английский

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PR-SET7 epigenetically restrains uterine interferon response and cell death governing proper postnatal stromal development

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

Опубликована: Июнь 10, 2024

Язык: Английский

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Quercetin ameliorates senescence and promotes osteogenesis of BMSCs by suppressing the repetitive element‑triggered RNA sensing pathway

International Journal of Molecular Medicine, Год журнала: 2024, Номер 55(1)

Опубликована: Окт. 22, 2024

Cell senescence impedes the self‑renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate role mechanism repetitive element (RE) activation BMSC osteogenesis, as well intervention effect quercetin. In an H2O2‑induced model, quercetin treatment alleviated shown by a decrease senescence‑associated β‑galactosidase (SA‑β‑gal)‑positive cell ratio, increased colony formation ability decreased mRNA expression p21 secretory phenotype genes. DNA damage response marker γ‑H2AX senescent BMSCs, while epigenetic markers methylation histone H3 Lys9, heterochromatin protein 1α heterochromatin‑related nuclear membrane lamina‑associated polypeptide 2 decreased. Quercetin rescued these alterations, indicating its ameliorate stabilizing structure where REs are primarily suppressed. Transcriptional accompanied accumulation cytoplasmic double‑stranded (ds)RNA, triggering RNA sensor retinoic acid‑inducible gene I (RIG‑I) receptor pathway BMSCs were shown. Similarly, inhibited responses. Additionally, RIG‑I knockdown led number SA‑β‑gal‑positive cells, confirming functional impact on senescence. Induction or administration dsRNA analogue significantly hindered reversed decline function. findings current demonstrated that sensing via regulation, thereby alleviating promoting osteogenesis.

Язык: Английский

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Interactions between human immunodeficiency virus and human endogenous retroviruses

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

ABSTRACT Human immunodeficiency virus (HIV), a retrovirus of the Lentivirus genus, targets CD4 + T cells, causing immune dysfunction and AIDS. Approximately 8% human genome consists endogenous retroviruses (HERVs), ancient retroviral remnants that may interact with HIV. Despite antiretroviral therapy, challenges such as drug resistance, poor reconstitution (PIR), reservoirs remain. This GEM discusses impact HIV on HERVs, potential roles HERVs in PIR reservoirs, provides insights into future research directions.

Язык: Английский

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Immune and vascular modulation by HERVs: the role of CXCR1 and IL18RAP in dengue severity progression

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

Introduction Human Endogenous Retroviruses (HERVs), which can be activated by viral infections, have complex roles in gene regulation and immune modulation. However, their contribution to disease progression is not yet fully understood. Dengue fever ranges from mild symptoms severe cases characterized plasma leakage dysregulation, providing a relevant context investigate these interactions. Methods This study comes up with comprehensive analysis of differentially expressed HERVs (DE-HERVs), protein-coding genes (DEGs), regulatory elements such as microRNAs (DE-miRNA) non-LTR retroviruses (DE-LINEs DE-SINEs) derived the transcriptomes Brazilian dengue patients across different stages. Results The results show that DE-HERVs are associated key identified cases, including ARG1, SLC15A2, COL3A1, SVEP1, CH25H, CST7 , CXCR1 IL18RAP, SORL1 TACR1 suggesting role modulation endothelial permeability. Specifically, upregulation IL18RAP who progressed correlates network involving down-regulated (miRNAs) retroviruses, emphasizing relevance inflammation vascular MicroRNAs were found regulate differently stages, appearing predominantly non-severe miRNA expression profiles varying comparison groups. Discussion These findings improve our understanding molecular mechanisms underlying suggest HERV-related networks may influence infections. Further research required clarify specific pathogenesis.

Язык: Английский

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