Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation [RNA-seq]

ABSTRACT: Aberrant DNA hypermethylation of promoter CpG islands in the context of a hypomethylated genome is a hallmark of cancer. Thus far there is no human experimental model available to mechanistically investigate this phenomenon. Here we show that upon reprogramming of human embryonic stem cells to the naïve state, the acquisition of a globally hypomethylated genome is accompanied by hypermethylation of a subset of bivalent promoter CpG islands, resulting in a DNA methylome comparable to the human inner cell mass. We show that de novo methylation is carried out by DNMT3A and coordinated by the transcription factor network. We further show that the subset of bivalent sites that become hypermethyated are functionally distinct, with an enrichment in developmental genes, and demonstrate that this is mirrored in DNA hypermethylation patterns across cancer types, suggesting that common mechanisms may be responsible. We propose a wider utility of this experimental system to understand pre-malignant cancer-associated processes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128287 | GEO | 2020/06/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (data set 4)

Project description:Aberrant DNA hypermethylation of promoter CpG islands in the context of a hypomethylated genome is a hallmark of cancer. Thus far there is no human experimental model available to mechanistically investigate this phenomenon. Here we show that upon reprogramming of human embryonic stem cells to the naïve state, the acquisition of a globally hypomethylated genome is accompanied by hypermethylation of a subset of bivalent promoter CpG islands, resulting in a DNA methylome comparable to the human inner cell mass. We show that de novo methylation is carried out by DNMT3A and coordinated by the transcription factor network. We further show that the subset of bivalent sites that become hypermethyated are functionally distinct, with an enrichment in developmental genes, and demonstrate that this is mirrored in DNA hypermethylation patterns across cancer types, suggesting that common mechanisms may be responsible. We propose a wider utility of this experimental system to understand pre-malignant cancer-associated processes.

2020-06-12 | GSE128128 | GEO

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (data set 3)

2020-06-12 | GSE128127 | GEO

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (data set 2)

2020-06-12 | GSE128126 | GEO

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (data set 1)

2020-06-12 | GSE128125 | GEO

Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome

Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.

2022-02-16 | PXD021821 | Pride

Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues

Project description:In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions in 24 tumor and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequent differentially methylated regions (DMRs) coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to cancer gene related silencing, however integration of publically available expression analysis shows that 75% of the frequently hypermethylation genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of colon cancer, comprehensive lists of DMRs, and gives further clues on the role of aberrant DNA methylation in CRC formation.

2012-10-26 | GSE39068 | GEO

Pan-cancer analysis revealed H3K4me1 at bivalent promoters premarks DNA hypermethylation during tumor development and identified the regulatory role of DNA methylation in relation to histone modifications [RRBS]

Project description:Background: DNA hypermethylation at promoter CpG islands (CGIs) is a hallmark of cancers and could lead to dysregulation of gene expression in the development of cancers, however, its dynamics and regulatory mechanisms remain elusive. Bivalent genes, that direct development and differentiation of stem cells, are found to be frequent targets of hypermethylation in cancers. Results: Here we performed comprehensive analysis across multiple cancer types and identified that the decrease in H3K4me1 levels coincides with DNA hypermethylation at the bivalent promoter CGIs during tumorigenesis. Removal of DNA hypermethylation leads to increment of H3K4me1 at promoter CGIs with preference for bivalent genes. Nevertheless, the alteration of H3K4me1 by overexpressing or knockout LSD1, the demethylase of H3K4, doesn't change the level or pattern of DNA methylation. Moreover, LSD1 was found to regulate the expression of a bivalent gene OVOL2 to promote tumorigenesis. Knockdown of OVOL2 in LSD1 knockout HCT116 cells restored the cancer cell phenotype. Conclusion: In summary, our work identified a universal indicator that can pre-mark DNA hypermethylation in cancer cells, and dissected the interplay between H3K4me1 and DNA hypermethylation in detail. Current study also reveals a novel mechanism underlying the oncogenic role of LSD1, providing clues for cancer therapies.

2023-01-12 | GSE222611 | GEO

2023-01-11 | GSE222612 | GEO