Elucidation of DNA Methylation on N6-Adenine with Deep Learning
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE149060 | GEO | 2020/04/22
REPOSITORIES: GEO
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Project description:In mammalian cells, DNA methylation on the 5th position of cytosine (5mC) plays an important role as an epigenetic mark. However, DNA methylation was considered to be absent in C. elegans because of the lack of detectable 5mC as well as homologs of the cytosine DNA methyltransferases. Here, using multiple approaches, we demonstrate the presence of adenine N6-methylation (6mA) in C. elegans DNA. We further demonstrate that this modification increases trans-generationally in a paradigm of epigenetic inheritance. Importantly, we identify a DNA demethylase, NMAD-1, and a potential DNA methyltransferase, DAMT-1, which regulate 6mA levels and crosstalk between methylation of histone H3K4me2 and 6mA, and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5. Together, these data identify a novel DNA modification in C. elegans and raise the exciting possibility that 6mA may be a carrier of heritable epigenetic information in eukaryotes. SMRT-sequencing for a mixed cell population of wildtype worms 6mA ChIP-Seq for a mixed cell population of wildtype worms
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Project description:DNA methylation on N6-adenine (6mA), the most prevalent DNA modification in prokaryotes, has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, the distribution patterns and potential functions of 6mA in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genomes of Arabidopsis thaliana Columbia-0 (Col), using single-molecule real-time sequencing. DNA methylome analysis shows that 6mA sites are widely distributed across the Col genomes and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies with a trend of enrichment around the transcriptional start site. In addition to a common consensus 6mA site found in other eukaryotes, novel 6mA sites were found, indicating that 6mA could evolve new functions in land plants. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA positively correlates with the gene expression level in Col plants. Consistently, DNA affinity chromatography coupled with mass spectrometry reveals that histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, indicating that 6mA could serve as a potentially novel epigenetic mark in land plants.
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Project description:DNA methylation on N6-adenine (6mA), the most prevalent DNA modification in prokaryotes, has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, the distribution patterns and potential functions of 6mA in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genomes of Arabidopsis thaliana Columbia-0 (Col), using single-molecule real-time sequencing. DNA methylome analysis shows that 6mA sites are widely distributed across the Col genomes and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies with a trend of enrichment around the transcriptional start site. In addition to a common consensus 6mA site found in other eukaryotes, novel 6mA sites were found, indicating that 6mA could evolve new functions in land plants. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA positively correlates with the gene expression level in Col plants. Consistently, DNA affinity chromatography coupled with mass spectrometry reveals that histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, indicating that 6mA could serve as a potentially novel epigenetic mark in land plants.
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Project description:DNA methylation on N6-adenine (6mA) has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genome of Arabidopsis thaliana using single-molecule real-time sequencing. 6mA sites are widely distributed across the Arabidopsis genome and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA frequency positively correlates with the gene expression level in Arabidopsis. Consistently, histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, suggesting that 6mA serves as a novel epigenetic mark in land plants.
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Project description:DNA methylation on N6-adenine (6mA) has recently been found as a potentially new epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain completely unknown. Here we report global profiling of 6mA sites at single-nucleotide resolution in the genome of Arabidopsis thaliana using single-molecule real-time sequencing. 6mA sites are widely distributed across the Arabidopsis genome and enriched over the pericentromeric heterochromatin regions. Nearly 30% of 6mA sites are present in gene bodies. Further analysis of 6mA methylome and RNA-sequencing data demonstrates that 6mA frequency positively correlates with the gene expression level in Arabidopsis. Consistently, histone variants associated with actively expressed genes interact with 6mA DNA. Our results uncover 6mA as a DNA mark associated with actively expressed genes in Arabidopsis, suggesting that 6mA serves as a novel epigenetic mark in land plants.
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Project description:In mammalian cells, DNA methylation on the 5th position of cytosine (5mC) plays an important role as an epigenetic mark. However, DNA methylation was considered to be absent in C. elegans because of the lack of detectable 5mC as well as homologs of the cytosine DNA methyltransferases. Here, using multiple approaches, we demonstrate the presence of adenine N6-methylation (6mA) in C. elegans DNA. We further demonstrate that this modification increases trans-generationally in a paradigm of epigenetic inheritance. Importantly, we identify a DNA demethylase, NMAD-1, and a potential DNA methyltransferase, DAMT-1, which regulate 6mA levels and crosstalk between methylation of histone H3K4me2 and 6mA, and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5. Together, these data identify a novel DNA modification in C. elegans and raise the exciting possibility that 6mA may be a carrier of heritable epigenetic information in eukaryotes.
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Project description:In human cells, 5-methylcytosine (5mC) DNA modification plays an important role in gene regulation. However, N6-methyladenine (6mA) DNA modification, which is predominantly present in prokaryotes, is considered to be absent in human genomic DNA. Here, using single molecule real-time (SMRT) sequencing on human blood, we show that DNA 6mA modification is extensively present in human genome, accounting for ~0.051% of the total adenines. [G/C]AGG[C/T] was the most significant motif associated with 6mA modification. 6mA sites are enriched in the exon coding regions and are associated with transcriptional activation. DNA N6-methyladenine and N6-demethyladenine modification in human are mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The 6mA abundance is significantly lower in cancer tissues compared to adjacent normal tissues, which is accompanied with decreased N6AMT1 and increased ALKBH1 levels. Decrease of 6mA modification level stimulated tumorigenesis in human. Collectively, our results demonstrate that 6mA DNA modification is present in human tissues, and we describe a potential role of the N6AMT1/ALKBH1-6mA regulatory axis in the progression of human cancer.
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