Altered Ten Eleven Translocation Methylcytosine Dioxygenase Expression and DNA Hydroxymethylation in a Mouse Model of Prostate Cancer [hMeDIP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1170307 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30917432.fastq.gz | Fastqsanger.gz | |||
| SRR30917433.fastq.gz | Fastqsanger.gz | |||
| SRR30917434.fastq.gz | Fastqsanger.gz | |||
| SRR30917435.fastq.gz | Fastqsanger.gz |
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Project description:Background: DNA hydroxymethylation (5hmC) is known to be altered in human prostate cancer. An animal model is required to study the functional roles of the Ten Eleven Translocation (TET) DNA dioxygenases and the 5hmC modification in prostate cancer development and progression. Methods: We characterized Tet expression, global genomic 5hmC, and genome-wide 5hmC patterns, and the transcriptome, in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) autochthonous model of prostate cancer. Results: We observed increased mRNA and protein expression of Tet1 in TRAMP samples, as compared to normal mouse prostate. Additionally, we found minimal expression of Tet2 mRNA overall, and Tet3 mRNA levels appeared similar in both sample types. However, TRAMP tumors expressed what appeared to be the inactive form of Tet3, versus the active form expressed in normal prostates. TRAMP tumors displayed global genomic hypohydroxymethylation (i.e., loss of 5hmC), and genome-wide analysis revealed widespread hypohydroxymethylation was interspersed with regions of locus specific hyperhydroxymethylation (i.e., increased 5hmC). The differentially hydroxymethylated regions correlated with altered gene expression, and pathway analyses indicated that these genes often participate in oncogenic pathways.Conclusions: Tet expression and 5hmC patterns are altered in the TRAMP model and closely match what has been observed in human prostate cancer, suggesting that TRAMP is a suitable model to study the role of Tets and 5hmC in prostate cancer development and progression.
2025-03-21 | GSE279076 | GEO
Project description:Altered Ten Eleven Translocation Methylcytosine Dioxygenase Expression and DNA Hydroxymethylation in a Mouse Model of Prostate Cancer [RNA-seq]
| PRJNA1170308 | ENA
Project description:Background: DNA hydroxymethylation (5hmC) is known to be altered in human prostate cancer. An animal model is required to study the functional roles of the Ten Eleven Translocation (TET) DNA dioxygenases and the 5hmC modification in prostate cancer development and progression. Methods: We characterized Tet expression, global genomic 5hmC, and genome-wide 5hmC patterns, and the transcriptome, in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) autochthonous model of prostate cancer. Results: We observed increased mRNA and protein expression of Tet1 in TRAMP samples, as compared to normal mouse prostate. Additionally, we found minimal expression of Tet2 mRNA overall, and Tet3 mRNA levels appeared similar in both sample types. However, TRAMP tumors expressed what appeared to be the inactive form of Tet3, versus the active form expressed in normal prostates. TRAMP tumors displayed global genomic hypohydroxymethylation (i.e., loss of 5hmC), and genome-wide analysis revealed widespread hypohydroxymethylation was interspersed with regions of locus specific hyperhydroxymethylation (i.e., increased 5hmC). The differentially hydroxymethylated regions correlated with altered gene expression, and pathway analyses indicated that these genes often participate in oncogenic pathways.Conclusions: Tet expression and 5hmC patterns are altered in the TRAMP model and closely match what has been observed in human prostate cancer, suggesting that TRAMP is a suitable model to study the role of Tets and 5hmC in prostate cancer development and progression.
2025-03-21 | GSE279077 | GEO
Project description:DNA hydroxymethylation plays a crucial role in the regulation of gene transcription. In this study, using hMeDIP-seq experiment, we report the mapping of DNA hydroxymethylation in adipocytes from mouse eWAT Examination of DNA hydroxymethylation pattern in adipocytes from mouse eWAT
2014-10-02 | E-GEOD-57582 | biostudies-arrayexpress
Project description:DNA hydroxymethylation plays a crucial role in the regulation of gene transcription. In this study, using hMeDIP-seq experiment, we report the mapping of DNA hydroxymethylation in adipocytes from mouse eWAT
2014-10-02 | GSE57582 | GEO
Project description:DNA hydroxymethylation (5hmC) represents a new layer of epigenetic regulation in addition to DNA methylation (5mC). The genome-wide patterns of 5hmC distribution in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, the DNA hydroxymethylome data generated by the conventional hMeDIP-seq method can not be used for direct quantitative comparison across different samples. In this study, we report a new quantitative hMeDIP-seq method, which uses barcode technology to label different DNA samples and performs hMeDIP-seq for multiple samples in one reaction system. Using this new method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESCs-derived neural progenitor cells (NPCs). 5hmC levels around TSS in either ESCs or NPCs had negative correlation with gene expression levels，while 5hmC levels at gene body regions had different correlation with gene expression, depending on cell types. We identified differential hydroxymethylated regions (DHMRs) by comparing the 5hmC density of all 5hmC peaks between ESCs and NPCs. Many selected DHMRs (e.g., Ankrd23, Hist1h2aa, Fbxw7, and Epha2) were validated by hMeDIP-qPCR. Furthermore, we analyzed the relationship between the alteration of DNA hydroxymethylation and the gene expression change during neural differentiation, and our data suggest that both up- and down-regulated genes exhibited dramatic decrease in 5hmC during neural differentiation while the alteration of 5hmC had weak positive correlation with the changes in gene expression. Taken together, our data demonstrate that quantitative hMeDIP-seq is a powerful approach for genome-wide comparison of DNA hydroxymethylation across multiple samples. Importantly, the DHMRs between ESCs and NPCs uncovered in this study may provide clues for further investigation of the function of 5hmC in gene regulation and neural differentiation. Comparision of the genome-wide distribution of 5hmC in mouse embryonic stem cells and mouse ES-derived neural progenitor cells.
2013-03-08 | E-GEOD-40810 | biostudies-arrayexpress
Project description:DNA hydroxymethylation (5hmC) represents a new layer of epigenetic regulation in addition to DNA methylation (5mC). The genome-wide patterns of 5hmC distribution in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, the DNA hydroxymethylome data generated by the conventional hMeDIP-seq method can not be used for direct quantitative comparison across different samples. In this study, we report a new quantitative hMeDIP-seq method, which uses barcode technology to label different DNA samples and performs hMeDIP-seq for multiple samples in one reaction system. Using this new method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESCs-derived neural progenitor cells (NPCs). 5hmC levels around TSS in either ESCs or NPCs had negative correlation with gene expression levels，while 5hmC levels at gene body regions had different correlation with gene expression, depending on cell types. We identified differential hydroxymethylated regions (DHMRs) by comparing the 5hmC density of all 5hmC peaks between ESCs and NPCs. Many selected DHMRs (e.g., Ankrd23, Hist1h2aa, Fbxw7, and Epha2) were validated by hMeDIP-qPCR. Furthermore, we analyzed the relationship between the alteration of DNA hydroxymethylation and the gene expression change during neural differentiation, and our data suggest that both up- and down-regulated genes exhibited dramatic decrease in 5hmC during neural differentiation while the alteration of 5hmC had weak positive correlation with the changes in gene expression. Taken together, our data demonstrate that quantitative hMeDIP-seq is a powerful approach for genome-wide comparison of DNA hydroxymethylation across multiple samples. Importantly, the DHMRs between ESCs and NPCs uncovered in this study may provide clues for further investigation of the function of 5hmC in gene regulation and neural differentiation.
2013-03-08 | GSE40810 | GEO
Project description:IntroductionIdentifying genetic factors that influence HIV-pathogenesis is critical for understanding disease pathways. Previous studies have suggested a role for the human gene ten-eleven methylcytosine dioxygenase 2 (TET2) in modulating HIV-pathogenesis.MethodsWe assessed whether genetic variation in TET2 was associated with markers of HIV-pathogenesis using both gene level and single nucleotide polymorphism (SNP) level association in 8512 HIV-positive persons across five clinical trial cohorts.ResultsVariation at both the gene and SNP-level of TET2 was found to be associated with levels of HIV viral load (HIV-VL) consistently in the two cohorts that recruited antiretroviral-naïve participants. The SNPs occurred in two clusters of high linkage disequilibrium (LD), one associated with high HIV-VL and the other low HIV-VL, and were predominantly found in Black participants.ConclusionGenetic variation in TET2 was associated with HIV-VL in two large antiretroviral therapy (ART)-naive clinical trial cohorts. The role of TET2 in HIV-pathogenesis warrants further investigation.
| S-EPMC9894145 | biostudies-literature
Project description:Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [hMeDIP]
| PRJNA913006 | ENA
Project description:Liver-specific ten-eleven translocation (Tet) methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a β-catenin target gene. HBV transcript abundance in adult Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several β-catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2, and Tbx3 in Tet-deficient mice were also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by β-catenin, these findings support the suggestion that neonatal Tet deficiency might limit β-catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine, a process that might be responsible for the reduction in cellular β-catenin target gene expression and viral transcription and replication.IMPORTANCEChronic hepatitis B virus (HBV) infection causes significant worldwide morbidity and mortality. There are no curative therapies available to resolve chronic HBV infections, and the small viral genome limits molecular targets for drug development. An alternative approach to drug development is to target cellular genes essential for HBV biosynthesis. In the liver, ten-eleven translocation (Tet) genes encode cellular enzymes that are not essential for postnatal mouse development but represent essential activities for viral DNA demethylation and transcription. Consequently, Tet inhibitors may potentially be developed into therapeutic agents capable of inducing and/or maintaining HBV covalently closed circular DNA methylation, resulting in transcriptional silencing and the resolution of chronic viral infection.
| S-EPMC10878274 | biostudies-literature