Heritable DNA methylation marks associated with susceptibility to breast cancer
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ABSTRACT:
PROVIDER: PRJNA414216 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide DNA Methylation analysis of 210 affected and unaffected individuals from 25 Australian families with multiple cases of breast cancer without carrying a mutation at breast cancer susceptibility genes. Genome-wide methylation was assessed using the Infinium HumanMethylation450K platform.
2017-10-14 | GSE104942 | GEO
Project description: Not available
| S-EPMC5830448 | biostudies-literature
Project description: Not available
| S-EPMC10275808 | biostudies-literature
Project description:Heritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are unknown. Here, we perform metabolic methyl-labelling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans. We find that methylation is transmitted to descendants in proteins, RNA, DNA and lipids. We further find that in response to parental starvation, naïve progeny display reduced fertility, increased heat stress resistance, and extended longevity. This intergenerational hormesis is accompanied by a heritable increase in N6’-dimethyl adenosine (m6,2A) on the 18S ribosomal RNA at adenosines 1735 and 1736. We identified DIMT-1 as the m6,2A methyltransferase in C. elegans and find that dimt-1 is required for the intergenerational hormesis phenotypes. Together this study provides the first labeling and tracking of heritable non-genetic material across generations and demonstrates the importance of rRNA methylation for regulating the heritable response to starvation
2022-05-01 | GSE175363 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE26018: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuEx-1_0-st] GSE26019: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuGene-1_0-st] GSE26038: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuEx-1_0-st, transcript] GSE26040: Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks Refer to individual Series
2011-03-31 | E-GEOD-26020 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of normal and methamphetamine (MA) abusers with different addiction susceptibility. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles in peripheral blood lymphocytes (PBLs). Samples included 8 health controls, 8 high MA addiction susceptibility (HMAS) abusers, and 8 high MA addiction susceptibility (LMAS) abusers.
2020-10-20 | GSE154971 | GEO
Project description:Background: Pulmonary arterial hypertension (PAH) and breast cancer disproportionately affect women. Bone morphogenetic protein receptor type 2 (BMPR2) mutations, the most common genetic cause of heritable PAH, also exert tumor-suppressive functions, yet their role in linking these diseases remains unclear. Methods: We combined bioinformatic, epidemiologic, and experimental approaches. Public cancer datasets were mined for BMPR2 alterations. In vivo, mammary tumor development and pulmonary hemodynamics were assessed in female Bmpr2⁺/Δ71 rats with or without carcinogen (DMBA) exposure. Pulmonary arterial smooth-muscle cells (PASMCs) were exposed to tumor-conditioned media to test inflammatory proliferation. Finally, associations between breast cancer and PAH were examined in the French National Healthcare Database (>9,000 PAH patients). Results: BMPR2 expression was markedly reduced in human breast tumors, with recurrent somatic variants and deep deletions identified. Bmpr2⁺/Δ71 rats exhibited spontaneous mammary tumors and, following DMBA exposure, developed exacerbated pulmonary hypertension with increased vascular remodeling and inflammation. Tumor-bearing Bmpr2⁺/Δ71 rats showed elevated lung IL-1β and NF-κB activation. In vitro, conditioned media from Bmpr2⁺/Δ71 tumors induced proliferation of Bmpr2⁺/Δ71 PASMCs via IL-1β-dependent signaling, while neutralization of IL-1β attenuated this effect. Human PASMCs carrying BMPR2 mutations similarly displayed heightened IL-1β-induced proliferation. Epidemiologically, breast cancer incidence was more than doubled in patients with PAH compared with the general population, and PAH incidence was increased nearly nine-fold among patients with breast cancer, indicating a bidirectional relationship. Conclusions: These findings identify a reciprocal association between breast cancer and PAH mediated by defective BMPR2 signaling and tumor-associated inflammation. Breast cancer may act as a “second hit” unmasking BMPR2-related susceptibility to PAH, underscoring BMPR2 as a shared molecular vulnerability with implications for surveillance of at-risk populations.
2026-02-25 | GSE314019 | GEO
Project description:The hypoxic tumor microenvironment (TME) is a common hallmark of solid cancers, including oral squamous cell carcinoma (OSCC). Hypoxia is predominantly regulated by the hypoxia-inducible factor-1 alpha (HIF-1α) and can alter the histone acetylation and methylation profile involved in drug resistance and possible therapeutic options for solid cancer. Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor (HDACi) that targets HIF-1α stability, whereas PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a thioredoxin-1 (Trx-1) inhibitor that prevents HIF-1α accumulation. Although HDACi are efficient in cancer treatment, they are accompanied by several adverse effects and increased resistance. This can be averted by combining HDACi with a Trx-1 inhibitor, as both inhibitors are connected by interlinked inhibitory pathways. HDACi inhibit Trx-1, leading to elevated reactive oxygen species (ROS) formation and death in cancerous cells; consequently, utilizing a Trx-1 inhibitor can boost the efficacy of HDACi. Previously, we investigated a synergistic interaction between vorinostat and PX-12 in an oral squamous carcinoma (OSCC) cell line under hypoxia. Here, we report to determine the effect of both inhibitors on histone acetylation and methylation expression levels under hypoxia in the CAL 27 cell line using mass spectrometry. We found several crucial histone marks, such as H3K4me1, H3K9ac, H3K9me, H3K14ac, H3K27me, H3K36me, H4K12Ac, and H4K16ac. The global analysis for histone acetylation and methylation and on specific residue shows their expression level was altered differentially by individual and combined inhibitor treatment. Our results provide an implication to investigate the underlying epigenetic mechanisms of histone acetylation and methylation levels in oral squamous cell carcinoma for a better understanding of developing drugs for cancer therapy.
2025-05-07 | PXD053244 | Pride
Project description:Incomplete reprogramming of organ-specific epigenetic marks during plant asexual reproduction leads to heritable phenotypic variation
| PRJEB26932 | ENA
Project description:Plants regenerated from tissue culture and their progenies are expected to be identical clones, but often display heritable molecular and phenotypic variation. We characterized DNA methylation patterns in callus, primary regenerants, and regenerant-derived progenies using immunoprecipitation of methylated DNA (meDIP) to assess the genome-wide frequency, pattern, and heritability of DNA methylation changes. Although genome-wide DNA methylation levels remained similar following tissue culture, numerous regions exhibited altered DNA methylation levels. Hypomethylation events were observed more frequently than hypermethylation following tissue culture. Many of the hypomethylation events occur at the same genomic site across independent regenerants and cell lines. The DNA methylation changes were often heritable in progenies produced from self-pollination of primary regenerants. Methylation changes were enriched in regions upstream of genes and loss of DNA methylation at promoters was associated with altered expression at a subset of loci. Differentially methylated regions (DMRs) found in tissue culture regenerants overlap with the position of naturally occurring DMRs more often than expected by chance with 8% of tissue culture hypomethylated DMRs overlapping with DMRs identified by profiling natural variation, consistent with the hypotheses that genomic stresses similar to those causing somaclonal variation may also occur in nature, and that certain loci are particularly susceptible to epigenetic change in response to these stresses. The consistency of methylation changes across regenerants from independent cultures suggests a mechanistic response to the culture environment as opposed to an overall loss of fidelity in the maintenance of epigenetic states.
2015-03-24 | GSE56479 | GEO