Genome-wide methylation and hydroxymethylcytosine pattern changes in basal-like breast cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA394235 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5827560.fastq.gz | Fastqsanger.gz | |||
| SRR5827561.fastq.gz | Fastqsanger.gz | |||
| SRR5827562.fastq.gz | Fastqsanger.gz | |||
| SRR5827555.fastq.gz | Fastqsanger.gz | |||
| SRR5827556.fastq.gz | Fastqsanger.gz |
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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 hydroxymethylcytosine pattern changes in response to oxidative stress
| PRJNA256032 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-07-05 | GSE101445 | 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.
2016-01-14 | GSE59718 | 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: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:Our understanding of the posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. Hydroxymethylcytosine, well described in DNA, occurs also in RNA, where its distribution, localization and function remain unexplored. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We provide the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We find that RNA hydroxymethylation can favor mRNA translation. Tet-deficient fruitflies show impaired brain development, accompanied by decreased RNA hydroxymethylation. Together, these steps into uncharted territory uncover central roles for RNA hydroxymethylation in Drosophila, highlighting the importance of epitranscriptomics.
2016-01-15 | GSE66090 | GEO
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.
2015-06-10 | GSE38791 | GEO
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.
2015-06-10 | GSE38790 | GEO