Similar Datasets
Project description:Ten eleven translocation enzymes (TET1-3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), inducing DNA demethylation and gene regulation. They are often downregulated in cancer, yet the upstream cause of this event remains largely unknown. Here, we show increased TET1 expression in basal-like breast cancer (BLBC), specifically in tumors with low expression of immune markers and low infiltration by immune cells. Furthermore, we identify an anti-correlation between TET1 expression and NF-κB, a major immune regulatory family, in BLBC tissues. In vitro and in vivo, TET1 is downregulated in breast cells upon activation of NF-κB, through binding of p65 to its consensus sequence in the TET1 promoter. Moreover, we uncover genome-wide 5hmC changes related to TET1 regulation in BLBC. Finally, these findings are extended to other cancer types, including melanoma, lung and thyroid cancers. Collectively, our data suggest a novel mode of regulation for TET1, linking TETs and immunity, two major features of cancer.
2018-07-05 | GSE101444 | GEO
Project description:Ten eleven translocation enzymes (TET1-3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), inducing DNA demethylation and gene regulation. They are often downregulated in cancer, yet the upstream cause of this event remains largely unknown. Here, we show increased TET1 expression in basal-like breast cancer (BLBC), specifically in tumors with low expression of immune markers and low infiltration by immune cells. Furthermore, we identify an anti-correlation between TET1 expression and NF-κB, a major immune regulatory family, in BLBC tissues. In vitro and in vivo, TET1 is downregulated in breast cells upon activation of NF-κB, through binding of p65 to its consensus sequence in the TET1 promoter. Moreover, we uncover genome-wide 5hmC changes related to TET1 regulation in BLBC. Finally, these findings are extended to other cancer types, including melanoma, lung and thyroid cancers. Collectively, our data suggest a novel mode of regulation for TET1, linking TETs and immunity, two major features of cancer.
2018-07-05 | GSE101443 | GEO
Project description:Genome-wide methylation and hydroxymethylcytosine pattern changes in basal-like breast cancer patients
| PRJNA394235 | ENA
Project description:The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in mice depleted for the major antioxidant enzymes GPx1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in coding genes, and intriguingly in microRNA genes, both involved in response to oxidative stress. These results thus suggest a profound effect of in vivo oxidative stress on the global hydroxymethylome.
| S-EPMC4523844 | biostudies-literature
Project description:The TET-family enzymes (TETs) convert methylcytosine to hydroxymethylcytosine, a lately discovered epigenetic modification that can modulate transcription. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain. Here we show that Tet1 is sensitive to peroxide and report a global decrease in hydroxymethylcytosine in cells treated with BSO and in the intestinal epithelium of mice lacking the major antioxidant enzymes glutathione peroxidases 1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in genes involved in responses to oxidative stress. Intriguingly, a considerable proportion of these regions lie in genes encoding microRNAs predicted to target transcripts involved in oxidative stress response. This work thus demonstrates a profound effect of oxidative stress on the hydroxymethylome and opens exciting new avenues of research by highlighting a set of microRNAs that may participate in the prevention or etiology of oxidative-stress-related diseases.
2016-01-14 | GSE59718 | GEO
Project description:Objective: The purpose of this study was to observe changes in DNA methylation in service members who experienced PTSD. Methods: We compared DNA Methylation profiles in the blood of those with or without PTSD and also compared those with PTSD at both baseline and follow-up with those service members that only developed PTSD at follow-up (3-months after baseline). Blood was collected and analyzed at baseline and follow up. Results: In participants with PTSD, 10 genes were significantly hyper-methylated and 18 were significantly hypo-methylated. In the second analysis, participants that had PTSD at both time points did not present any differentially methylated gene regions. Interestingly, for individuals’ whose PTSD scores increased from baseline to follow-up, there were 8 hypo-methylated genes detected at the baseline.
2018-06-14 | GSE93673 | GEO
Project description:The TET-family enzymes (TETs) convert methylcytosine to hydroxymethylcytosine, a lately discovered epigenetic modification that can modulate transcription. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain. Here we show that Tet1 is sensitive to peroxide and report a global decrease in hydroxymethylcytosine in cells treated with BSO and in the intestinal epithelium of mice lacking the major antioxidant enzymes glutathione peroxidases 1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in genes involved in responses to oxidative stress. Intriguingly, a considerable proportion of these regions lie in genes encoding microRNAs predicted to target transcripts involved in oxidative stress response. This work thus demonstrates a profound effect of oxidative stress on the hydroxymethylome and opens exciting new avenues of research by highlighting a set of microRNAs that may participate in the prevention or etiology of oxidative-stress-related diseases. Examination of DNA hydroxymethylation landscape in SY5Y cell lines and in intestinal epithelium of mice.
2016-01-14 | E-GEOD-59718 | biostudies-arrayexpress
Project description:Embryonic stem cells upon extrinsic induction could self-assemble into blastocyst-like structures. However, the intrinsic regulation of such blastoid forming potential remain to be addressed. We discover that the activity of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) in expanded potential stem cell (EPSC) positively correlates with blastoid efficiency and quality. In addition, Nr1h2 agonist, T0901317, improves natural blastocyst development. Surprisingly, Nr1h2-activated ESC (NrESC) is rewired towards a distinct pluripotency state that is capable of self-organizing into blastoids and contribute to embryonic and extraembryonic lineage. We hypothesize that Nr1h2 activation broadly affects the DNA methylation to rewire ESC state. Indeed, from WGBS data, we observe that genome-wide DNA methylation differences in NrESC or EPSC after treated with T09 . In summary, our study demonstrates a novel Nr1h2-centric regulation of expanded pluripotency.
2024-10-23 | GSE244019 | GEO
Project description:Discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes has excited the field of epigenetics, but information on the genome-wide distribution of 5hmC is limited. Globozoospermia is a rare but severe cause of male infertility. To date, the epigenetic mechanism, especially 5hmC profiles involved in globozoospermia progression, remains largely unknown. Here, utilizing the chemical labeling and biotin-enrichment approach followed by Illumina HiSeq sequencing, we showed that (i) 6664, 9029 and 6318 genes contain 5hmC in normal, abnormal, and globozoospermia sperm, respectively; (ii) some 5hmC-containing genes significantly involves in spermatogenesis, sperm motility and morphology, and gamete generation; (iii) 5hmC is exclusively localized in sperm intron; (iv) approximately 40% imprinted genes have 5hmC modification in sperm genomes, but globozoospermia sperm exhibiting a large portion of imprinted genes lose the 5hmC modification; (v) six imprinted genes showed different 5hmC patterns in abnormal sperm (GDAP1L1, GNAS, KCNK9, LIN28B, RB1, RTL1), and five imprinted genes showed different 5hmC patterns in globozoospermia sperm (KCNK9, LIN28B, RB1, SLC22A18, ZDBF2). These results suggested that differences in genome-wide 5hmC patterns may in part be responsible for the sperm phenotype. All of this may improve our understanding of the basic molecular mechanism underlying sperm biology and the etiology of male infertility.
| S-EPMC4466632 | biostudies-literature
Project description:Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress
| PRJNA256032 | ENA