Non-canonical base modifications of bacterial origin in a eukaryotic genome [MeDIP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA588094 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10408994.fastq.gz | Fastqsanger.gz | |||
| SRR10408995.fastq.gz | Fastqsanger.gz | |||
| SRR10408996.fastq.gz | Fastqsanger.gz | |||
| SRR10408997.fastq.gz | Fastqsanger.gz |
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Project description:Methylation of cytosines at the 5th carbon position of the aromatic ring has long been regarded as the predominant type of DNA base modification in eukaryotes. Often called “the fifth base”, C5-methylcytosine (5mC) plays an important role in genome defense against mobile genetic elements, and is mostly associated with transcriptional silencing, establishment of the closed chromatin configuration, and repressive histone modifications. Recently, another type of DNA modification, N6-methyladenine (6mA), has been added to the repertoire of modified bases in eukaryotic DNA, and was mostly linked to elevated transcription levels. In prokaryotes, 5mC and 6mA typically constitute components of restriction-modification (R-M) systems, along with N4-methylcytosine (4mC), which so far has been confined to bacteria. Here we report the first case of 4mC occurrence in eukaryotic DNA. We find that bdelloid rotifers, small freshwater invertebrates known for their ability to reproduce clonally and to acquire genes from non-metazoan sources, lack the canonical eukaryotic C5-methyltransferases but instead encode an amino-methyltransferase of bacterial origin, N4CMT, which is present in all bdelloid families separated by tens of millions of years of evolution. The recombinant N4CMT introduces 4mC into genomic DNA in vivo and in vitro. Using SMRT-seq (PRJNA558051), MeDIP-seq, ChIP-seq, and RNA-seq, we examined genome-wide distribution of non-canonical base modifications over annotated genomic features and observed an excess of 4mC in silenced transposable elements and certain tandem repeats, while 6mA tends to associate with transcribed genes and active chromatin. The presence of the chromodomain in N4CMT explains its affinity for repressive histone marks, H3K9me3 and especially H3K27me3. Our results expand the known repertoire of eukaryotic base modifications, shed light on the process of recruitment of methyl groups as epigenetic marks in DNA, and highlight the role of horizontal gene transfer as an important driver of evolutionary innovation in eukaryotes.
2022-01-07 | GSE140050 | GEO
Project description:Methylation of cytosines at the 5th carbon position of the aromatic ring has long been regarded as the predominant type of DNA base modification in eukaryotes. Often called “the fifth base”, C5-methylcytosine (5mC) plays an important role in genome defense against mobile genetic elements, and is mostly associated with transcriptional silencing, establishment of the closed chromatin configuration, and repressive histone modifications. Recently, another type of DNA modification, N6-methyladenine (6mA), has been added to the repertoire of modified bases in eukaryotic DNA, and was mostly linked to elevated transcription levels. In prokaryotes, 5mC and 6mA typically constitute components of restriction-modification (R-M) systems, along with N4-methylcytosine (4mC), which so far has been confined to bacteria. Here we report the first case of 4mC occurrence in eukaryotic DNA. We find that bdelloid rotifers, small freshwater invertebrates known for their ability to reproduce clonally and to acquire genes from non-metazoan sources, lack the canonical eukaryotic C5-methyltransferases but instead encode an amino-methyltransferase of bacterial origin, N4CMT, which is present in all bdelloid families separated by tens of millions of years of evolution. The recombinant N4CMT introduces 4mC into genomic DNA in vivo and in vitro. Using SMRT-seq (PRJNA558051), MeDIP-seq, ChIP-seq, and RNA-seq, we examined genome-wide distribution of non-canonical base modifications over annotated genomic features and observed an excess of 4mC in silenced transposable elements and certain tandem repeats, while 6mA tends to associate with transcribed genes and active chromatin. The presence of the chromodomain in N4CMT explains its affinity for repressive histone marks, H3K9me3 and especially H3K27me3. Our results expand the known repertoire of eukaryotic base modifications, shed light on the process of recruitment of methyl groups as epigenetic marks in DNA, and highlight the role of horizontal gene transfer as an important driver of evolutionary innovation in eukaryotes.
2022-01-07 | GSE140051 | GEO
Project description:Methylation of cytosines at the 5th carbon position of the aromatic ring has long been regarded as the predominant type of DNA base modification in eukaryotes. Often called “the fifth base”, C5-methylcytosine (5mC) plays an important role in genome defense against mobile genetic elements, and is mostly associated with transcriptional silencing, establishment of the closed chromatin configuration, and repressive histone modifications. Recently, another type of DNA modification, N6-methyladenine (6mA), has been added to the repertoire of modified bases in eukaryotic DNA, and was mostly linked to elevated transcription levels. In prokaryotes, 5mC and 6mA typically constitute components of restriction-modification (R-M) systems, along with N4-methylcytosine (4mC), which so far has been confined to bacteria. Here we report the first case of 4mC occurrence in eukaryotic DNA. We find that bdelloid rotifers, small freshwater invertebrates known for their ability to reproduce clonally and to acquire genes from non-metazoan sources, lack the canonical eukaryotic C5-methyltransferases but instead encode an amino-methyltransferase of bacterial origin, N4CMT, which is present in all bdelloid families separated by tens of millions of years of evolution. The recombinant N4CMT introduces 4mC into genomic DNA in vivo and in vitro. Using SMRT-seq (PRJNA558051), MeDIP-seq, ChIP-seq, and RNA-seq, we examined genome-wide distribution of non-canonical base modifications over annotated genomic features and observed an excess of 4mC in silenced transposable elements and certain tandem repeats, while 6mA tends to associate with transcribed genes and active chromatin. The presence of the chromodomain in N4CMT explains its affinity for repressive histone marks, H3K9me3 and especially H3K27me3. Our results expand the known repertoire of eukaryotic base modifications, shed light on the process of recruitment of methyl groups as epigenetic marks in DNA, and highlight the role of horizontal gene transfer as an important driver of evolutionary innovation in eukaryotes.
2022-01-07 | GSE140049 | GEO
Project description:Non-canonical base modifications of bacterial origin in a eukaryotic genome
| PRJNA588087 | ENA
Project description:Non-canonical base modifications of bacterial origin in a eukaryotic genome [RNA-seq]
| PRJNA588092 | ENA
Project description:Non-canonical base modifications of bacterial origin in a eukaryotic genome [ChIP-seq]
| PRJNA588089 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-07 | GSE140052 | GEO
Project description:In this study, we have developed MB-seq, a novel DNA methylome profiling technology combining MeDIP-seq with bisulfite conversion, which can precisely detect the 5mC sites and determine their DNA methylation level at single-base resolution in a cost-effective way. In addition, we have developed a new alternative method, MRB-seq (MeDIP-repetitive elements removal-bisulfite sequencing), which interrogates 5mCs in functional regions by depleting nearly half of repeat fragments enriched by MeDIP. Comparing MB-seq and MRB-seq to whole-genome BS-seq using the same batch of DNA from YH peripheral blood mononuclear cells. We found that the sequencing data of MB-seq and MRB-seq almost reaches saturation after generating 7-8 Gbp data, whereas BS-seq requires about 100 Gbp data to achieve the same effect. In comparison to MeDIP-seq and BS-seq, MB-seq offers several key advantages, including single-base resolution, discriminating the methylated sites within a CpG and non-CpG pattern and overcoming the false positive of MeDIP-seq due to the non-specific binding of 5-methylcytidine antibody to genomic fragments.
2017-08-17 | GSE94071 | GEO
Project description:Chromosome 3p monosomy is associated with a poor clinical outcome of patients with uveal melanoma. Since a copy of the tumor suppressor miR-16 gene is lost for these patients, we postulated that a 3p loss may reduce the miR-16 amount and activity, promoting RNA derepression and tumor burden (loss of brake effect) as observed in chronic lymphocytic leukemia. Unexpectedly, we found that miR-16 expression level is not decreased despite the 3p monosomy. In contrast, our results suggested that miR-16 activity is impaired in uveal melanoma. Here, we investigated the molecular mechanism explaining the sequestration of miR-16 by RNAs. By defining the miR-16 interactome, two genes sets have been highlighted, suggesting two divergent miR-16 functions. In addition to the canonical miR-16 targets such as CCND3 and CDC25A, we identified another set of miR-16-interacting RNAs called thereafter miR-16 sponges. miR-16 binds to these RNAs sponge without inducing their decay. Mechanistically, the miR-16/RNA non-canonical base-pairing promoted stability of mRNAs involved in cancer cell proliferation. The biological relevance has been challenged in uveal melanoma. We showed that patients with poor overall survival expressed higher levels of miR-16 sponges and canonical miR-16 targets. These results strongly suggested that miR-16 is no longer able to repress its targets and, in contrast, promotes RNA stability and protein expression of oncogenes. miR-16 activity assessment using our Sponge-signature discriminates the patient’s overall survival as efficiently as the current method based on copy number variations and driver mutations detection. To conclude, miRNA loss of function due miRNA sequestration seems to promote cancer burden by two combined events – “loss of brake and an acceleration”. Our results highlight the oncogenic role of the non-canonical base-pairing between miRNAs/mRNAs in uveal melanoma.
2022-10-05 | GSE180399 | GEO
Project description:Using bottom-up oligonucleotide LC-MS/MS in combination with stable isotope labeling, chemical derivatization, and bioinformatics variable modification search, a total of 25 modifications were mapped to the sequences of 16S and 23S RNA in B. subtilis. 10 modification sites, previously identified by others using alternative methods were independently confirmed using targeted MS/MS data analysis. Modification types, namely base/ribose methylation, pseudouridines and dihydrouridine, and modification positions are fully consistent with prior experimental evidence and agree well with modifications that were annotated in E. coli and other bacteria species.
2024-08-06 | PXD050367 | Pride