Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222611 | GEO | 2023/01/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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 [ChIP-seq]

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 | GSE222523 | GEO

2023-01-12 | GSE222521 | GEO

2023-01-11 | GSE222612 | GEO

De novo DNA methylation at imprinted loci during reprogramming into naïve and primed pluripotency

Project description:CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during the somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, were often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs.

2019-06-18 | GSE111173 | GEO

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

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

2020-06-12 | GSE128287 | GEO

Oct4-mediated inhibition of Lsd1 activity promotes the active and primed state of pluripotency enhancers [methylRAD-seq]

Project description:Enhancer reactivation and pluripotency gene (PpG) expression could induce stemness and enhance tumorigenicity in cancer stem cells. Silencing of PpG enhancers (PpGe) during embryonic stem cell differentiation involves Lsd1–mediated H3K4me1 demethylation followed by DNA methylation. Here, we observed a widespread retention of H3K4me1 and DNA hypomethylation at PpGe associated with a partial repression of PpGs in F9 embryonal carcinoma cells (ECCs) post-differentiation. The absence of H3K4me1 demethylation could not be rescued by Lsd1 overexpression. Based on the observation that H3K4me1 demethylation is accompanied by strong Oct4 repression in P19 ECCs, we tested if Lsd1-Oct4 interaction affects Lsd1 catalytic activity. Our data show a dose-dependent inhibition of Lsd1 by Oct4 in vitro and retention of H3K4me1 at PpGe post-differentiation in Oct4 overexpressing P19 ECCs. These data suggest that Lsd1-Oct4 interaction in cancer stem cells may establish a primed enhancer state that is susceptible to reactivation leading to aberrant PpG expression.

2020-06-29 | GSE135226 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data