Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands

ABSTRACT: Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for involvement of low transcription and trimethylation of histone H3 lysine 27 (H3K27me3). Here, we used methylated DNA immunoprecipitation (MeDIP) combined with a CGI oligonucleotide microarray analysis, and identified 5510 and 521 genes with promoter CGIs resistant and susceptible, respectively, to DNA methylation in prostate cancer cell lines. Expression analysis revealed that the susceptible genes had low transcription in a normal prostatic epithelial cell line. Chromatin immunoprecipitation with microarray hybridization (CHiP-chip) analysis of RNA polymerase II (Pol II) and histone modifications showed that, even among the genes with low transcription, the presence of Pol II was associated with marked resistance to DNA methylation (OR = 0.22; 95% CI = 0.12-0.38), and H3K27me3 was associated with increased susceptibility (OR = 11.20; 95% CI = 7.14-17.55). The same was true in normal human mammary epithelial cells for 5430 and 733 genes resistant and susceptible, respectively, to DNA methylation in breast cancer cell lines. These results showed that the presence of Pol II, active or stalled, and H3K27me3 can predict the epigenetic fate of promoter CGIs independently of transcription levels.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15154 | GEO | 2009/07/31

SECONDARY ACCESSION(S): PRJNA114921

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands.

Project description:Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for involvement of low transcription and trimethylation of histone H3 lysine 27 (H3K27me3). Here, we used methylated DNA immunoprecipitation (MeDIP) combined with a CGI oligonucleotide microarray analysis, and identified 5510 and 521 genes with promoter CGIs resistant and susceptible, respectively, to DNA methylation in prostate cancer cell lines. Expression analysis revealed that the susceptible genes had low transcription in a normal prostatic epithelial cell line. Chromatin immunoprecipitation with microarray hybridization (CHiP-chip) analysis of RNA polymerase II (Pol II) and histone modifications showed that, even among the genes with low transcription, the presence of Pol II was associated with marked resistance to DNA methylation (OR = 0.22; 95% CI = 0.12-0.38), and H3K27me3 was associated with increased susceptibility (OR = 11.20; 95% CI = 7.14-17.55). The same was true in normal human mammary epithelial cells for 5430 and 733 genes resistant and susceptible, respectively, to DNA methylation in breast cancer cell lines. These results showed that the presence of Pol II, active or stalled, and H3K27me3 can predict the epigenetic fate of promoter CGIs independently of transcription levels. To analyze DNA methylation status in normal and cancer cells, MeDIP-CGI oligonucleotide microarray analysis was performed. To analyze expression and histone modification status in normal cells, GeneChip analysis and ChIP-oligonucleotide microarray analysis were performed.

2010-05-15 | E-GEOD-15154 | biostudies-arrayexpress

Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.

Project description:Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33-15.34) and from LINE (OR=2.08; 95% CI=1.03-4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02-0.48) and H3K27me3 (OR=3.28; 95% CI=1.17-9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.

2011-06-06 | GSE28284 | GEO

The Polycomb group mutant esc leads to augmented the levels of paused Pol II in the Drosophila embryo.

Project description:The role of Polycomb group (PcG) was studied on RNA Polymerase II (Pol II) pausing phenomenon. Wild type and Polycomb mutant (esc) embryos were used for ChIP-Seq experiments using Pol II and histone methylation antibodies. Enhanced Pol II occupancy was observed for thousands of genes in esc mutant embryos, including genes not known to be bound by PRC2 or having H3K27me3 associated. Most of these genes exhibit a concomitant reduction in H3K27me3 and increase in H3K4me3 at promoter-proximal regions. Silent genes lacking promoter-associated paused Pol II in wild-type embryos are converted into âpoisedâ genes with paused Pol II in esc mutants. We suggest that this conversion of silent genes into poised genes might render differentiated cell types susceptible to switches in identity in PcG mutants. ChIP-Seq data was generated for antibodies against Pol-II, H3K4me3, H3K27me3 in both wild type and esc mutant Drosophila embryos (0-2hr, 8-12hr, and 18-24hr embryos). In addition GRO-Seq data was generated for 18-24hr esc mutant embryos.

2011-06-14 | E-GEOD-28833 | biostudies-arrayexpress

The Polycomb group mutant esc leads to augmented the levels of paused Pol II in the Drosophila embryo.

2011-06-15 | GSE28833 | GEO

Genome-wide analysis of next generation sequencing for Lsh+/+ and Lsh-/- mouse embryonic fibroblasts

Project description:To examine the relationship of reduced CG methylation and gene expression in Lsh KO MEFs, we computed mean CG methylation levels at promoter regions of protein-coding genes. About 60% of TSS regions of protein-coding genes display a difference of CG methylation values greater than 0.3 (WT CG methylation minus KO CG methylation) indicating that Lsh deletion has widespread effects at promoter regions. RNA-seq analysis detects similar transcript steady state levels in WT and KO samples. To determine the relationship of Pol II binding and CG methylation reduction in KO MEFs, Pol II Chip-seq was performed. Protein coding genes were ranked according their CG methylation differences between WT MEFs and KO MEFs. The greatest loss of CG methylation is found at promoter with low CG density. Pol II association is inversely related to the number of CpG sites within promoter regions. KO MEFs show less Pol II association at CG rich promoter regions. However, RNA-seq reads are indistinguishable comparing WT and KO samples, suggesting similar transcriptional efficiency in the absence of Lsh. To explore other molecular mechanisms that may preserve low transcription activity or repression at CG hypomethylated promoter regions, we examined H3K27me3 and H3K4me3 modifications by ChIP-seq. Genome wide computation of histone modifications at 5kb tiles shows no increase of H3K27me3 level in KO MEFs. When we ranked 5kb tiles based on CG methylation differences between WT and KO, we observed alterations in H3K27me3 distribution, while H3K4me3 modifications are unremarkable. Regions with moderate CG methylation reduction exhibit concomitant decreases in H3K27me3. mRNA profiles and Genome-wide maps of H3K27me3, H3K4me3 and Pol II in wildtype (WT) and Lsh KO primary MEFs.

2014-06-24 | E-GEOD-57419 | biostudies-arrayexpress

Chromatin IP for H3 K27me3 modified histone tails in the liver of control mice, Phenobarbital exposed mice and a resulting Ctnnb1 mutated PB liver tumour [ChIP-seq]

Project description:Through the analysis of mouse liver tumours promoted by distinct routes (DEN exposure alone, DEN exposure plus non-genotoxic insult with phenobarbital and non-alcoholic fatty liver disease); we report that the cancer associated hyper-methylated CGI events in mice are also predicated by silent promoters that are enriched for both the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone modification H3K27me3 in normal liver. During cancer progression these CGIs undergo hypo-hydroxymethylation, prior to subsequent hyper-methylation; whilst retaining H3K27me3. A similar loss of promoter-core 5hmC is observed in Tet1 deficient mouse livers indicating that reduced Tet1 binding at CGIs may be responsible for the epigenetic dysregulation observed during hepatocarcinogenesis. Consistent with this reduced Tet1 protein levels are observed in mouse liver tumour lesions. As in human, DNA methylation changes at CGIs do not appear to be direct drivers of hepatocellular carcinoma progression in mice. Instead dynamic changes in H3K27me3 promoter deposition are strongly associated with tumour-specific activation and repression of transcription. Our data suggests that loss of promoter associated 5hmC in diverse liver tumours licences DNA methylation reprogramming at silent CGIs during cancer progression. We carry out Chromatin immunoprecipitation (ChIP) prior to sequencing on Illumina Hiseq 2500 to report on the genome-wide H3K27me3 patterns in normal mouse liver, 12 week Phenobarbital exposed mouse livers and 35 week pehonbarbital exposed liver tumours.

2016-05-17 | E-GEOD-77728 | biostudies-arrayexpress

Comprehensive analysis of orphan CpG islands identifes novel promoters with conserved DNA methylation dynamics

Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues. Examination of CGI methylation status in human and mouse primary tissues.

2010-10-04 | E-GEOD-21442 | biostudies-arrayexpress

The PRC2-associated factor C17orf96 is a novel CpG island regulator in mouse ES cells

Project description:CpG islands (CGIs) are key DNA regulatory elements in the vertebrate genome and are often found at gene promoters. In mammalian embryonic stem (ES) cells, CGIs are decorated by either the active or repressive histone marks, H3K4me3 and H3K27me3, respectively, or by both modifications (‘bivalent domains’), but their precise regulation is incompletely understood. Remarkably, we find that the polycomb repressive complex 2 (PRC2)-associated protein C17orf96 (a.k.a. esPRC2p48 and E130012A19Rik) is present at most CGIs in mouse ES cells. At PRC2-rich CGIs, loss of C17orf96 results in an increased chromatin binding of Suz12 and elevated H3K27me3 levels concomitant with gene repression. In contrast, at PRC2-poor CGIs, located at actively transcribed genes, C17orf96 colocalizes with RNA polymerase II and its depletion leads to a focusing of H3K4me3 in the core of CGIs. Our findings thus identify C17orf96 as a novel context-dependent CGI regulator. ChIP-seq of C17orf96, H3K4me3 and H3K27me3 in mouse ES cells (E14).

2015-04-29 | E-GEOD-63491 | biostudies-arrayexpress

In uveal melanoma Gα-protein GNA11 mutations convey a shorter disease-specific survival and are more strongly associated with loss of BAP1 and chromosomal alterations than Gα-protein GNAQ mutations

Project description:Mutations in the Gα-genes GNAQ and GNA11 are found in 85-90% of uveal melanomas (UMs). We analyzed the association between GNAQ and GNA11 mutations with disease-specific survival, gene expression profiles, and cytogenetic alterations in 219 UMs. Our analysis showed a shorter disease-specific survival of GNA11-mutated cases as compared to those carrying a GNAQ mutation (HR=1.97 [95%CI 1.12-3.46], p=0.02). GNA11 mutated UMs displayed a shorter, but not significant, median months survival of 26.97 [95% CI 25.02-37.08] versus GNAQ patients median months survival of 31.5 [95% CI 30.97-53.51]. The GNA11 mutation was also associated with: i) an increased frequency of loss of BRCA1-associated protein 1 (BAP1) expression (p=0.0005), ii) monosomy of chromosome 3 (p<0.001), iii) amplification of chr8q (p=0.038), iv) the combination of the latter two (p=0.0002), and inversely with v) chr6p gain (p=0.003). We used tandem-affinity-purification and mass spectrometry to show that the two derived G-proteins have different protein interaction partners. Specifically, the Tet Methylcytosine Dioxygenase 2(TET2), a protein that is involved in DNA demethylation, physically interacts with the GNAQ protein but not with GNA11, as confirmed by immunoprecipitation analyses. High-risk UM cases show a clearly different DNA-methylation pattern, suggesting that a different regulation of DNA methylation by the two G-proteins might convey a different risk of progression.

2023-02-27 | GSE197656 | GEO

IP of 5-methylcytosine (5-mc) enriched DNA fragments from control and mice with non-acoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC)

2016-05-17 | GSE77725 | GEO