CG dinucleotides enhance promoter activity independent of DNA methylation
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ABSTRACT:
PROVIDER: PRJNA479961 | ENA |
REPOSITORIES: ENA
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Project description:Most mammalian RNA Polymerase II initiation events occur at CpG islands, which are rich in CpGs and devoid of DNA methylation. Despite their relevance for gene regulation, it is unknown to what extent the CpG dinucleotide itself actually contributes to promoter activity. To address this question, we determined the transcriptional activity of a large number of chromosomally integrated promoter constructs and monitored binding of transcription factors assumed to play a role in CpG island activity. This revealed that CpG density significantly improves motif-based prediction of transcription factor binding. Our experiments also show that high CpG density alone is insufficient for transcriptional activity, yet results in increased transcriptional output when combined with particular transcription factor motifs. Yet, this CpG contribution to promoter activity is independent of DNA methyltransferase activity. Together this refines our understanding of mammalian promoter regulation as it shows that high CpG density within CpG islands directly contributes to an environment permissive for full transcriptional activity.
2019-01-20 | GSE116704 | GEO
Project description: Not available
| S-EPMC6442381 | biostudies-literature
Project description:Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints. DNA methylation, RNA and nucleosome sequencing data for diverse eukaryotes
2014-03-13 | E-GEOD-46692 | biostudies-arrayexpress
Project description:Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.
2014-03-13 | GSE46692 | GEO
Project description:Vertebrate genomes exhibit marked CG-suppression, that is lower than expected numbers of 5’-CG-3’ dinucleotides1. This feature is likely due to C-to-T mutations that have accumulated over hundreds of millions of years, driven by CG-specific DNA methyl transferases and spontaneous methyl-cytosine deamination. Remarkably, many RNA viruses of vertebrates that are not substrates for DNA methyl transferases mimic the CG-suppression of their hosts2-4. This striking property of viral genomes is unexplained4-6. In a synonymous mutagenesis experiment, we found that CG-suppression is essential for HIV-1 replication. The deleterious effect of CG dinucleotides on HIV-1 replication was cumulative, evident as cytoplasmic RNA depletion, and exerted by CG dinucleotides in both translated and non-translated exonic RNA sequences. A focused siRNA screen revealed that zinc finger antiviral protein (ZAP)7 inhibited virion production by cells infected with CG-enriched HIV-1. Crucially, HIV-1 mutants containing segments whose CG-content mimicked random sequence were defective in unmanipulated cells, but replicated normally in ZAP-deficient cells. Crosslinking-immunoprecipitation-sequencing assays demonstrated that ZAP binds directly and selectively to RNA sequences containing CG dinucleotides. These findings suggest that ZAP exploits host CG-suppression to discriminate non-self RNA. The dinucleotide composition of HIV-1, and perhaps other RNA viruses, appears to have adapted to evade this host defense.
2017-08-22 | GSE102843 | GEO
Project description:Dnmt1-Independent CG Methylation Contributes to Nucleosome Positioning in Diverse Eukaryotes
| PRJNA201680 | ENA
Project description:DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpC and CpT dinucleotides. Here we report a comprehensive analysis of non-CG methylation in 72 genome-scale DNA methylation maps across human pluripotent and differentiated cell types. We confirm non-CG methylation to be predominant in pluripotent cell types and observe an expected decrease upon differentiation and near complete absence in various differentiated cells. Our data highlight that non-CG methylation is highly variable and shows little conservation between different pluripotent cell lines. While we show a strong correlation of non-CG methylation and DNMT3 expression levels we find a statistical independence of non-CG methylation from pluripotency associated gene expression. Finally, non-CG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of DNA methylation in human cells and help clarify previous observations using a large representative sample set. Examination of nonCG DNA methylation patterns in pluripotent and differentiated cells
2011-08-31 | E-GEOD-27432 | biostudies-arrayexpress
Project description:DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpC and CpT dinucleotides. Here we report a comprehensive analysis of non-CG methylation in 72 genome-scale DNA methylation maps across human pluripotent and differentiated cell types. We confirm non-CG methylation to be predominant in pluripotent cell types and observe an expected decrease upon differentiation and near complete absence in various differentiated cells. Our data highlight that non-CG methylation is highly variable and shows little conservation between different pluripotent cell lines. While we show a strong correlation of non-CG methylation and DNMT3 expression levels we find a statistical independence of non-CG methylation from pluripotency associated gene expression. Finally, non-CG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of DNA methylation in human cells and help clarify previous observations using a large representative sample set.
2011-09-01 | GSE27432 | GEO
Project description:Evaluation of CG-100 Intraluminal Bypass device
| 1009 | ecrin-mdr-crc
Project description:Cytosine methylation is commonly targeted to symmetrical CG sites, as well as to non-CGs, such as the symmetrical-CHG and asymmetric-CHH sites in plants (H= A, C or T). Thus far, depletion of CG methylation in plants was associated with ample transcriptional activation of transposons. Here, we profiled transcription in various context specific methylation mutants in the early-diverged plant, Physcomitrella patens. We discovered that specific elimination of CG methylation is fully complemented by non-CG methylation but not vice versa. Between the symmetrically-methylated sites, CHG methylation silenced transposons stronger than CG methylation did. Finally, non-CG methylation revealed as crucial for the silencing of CG depleted transposons. Our results suggest that non-CG methylation evolved to silence transposons due to functional limitations and/or rapid mutability of methylated-CGs.
2020-12-30 | GSE142053 | GEO