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Identify the interplay between N6-methyladenine and gene regulation under hypoxia by randomized empirical model (ChIP-seq)

ABSTRACT: In this study, we employed ChIP-seq for histone modifications related to gene activation, such as H3K4me1, H3K4me3, and H3K27Ac, to investigate the role of N6-methyladenine (6mA) in chromatin accessibility under hypoxic conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE260871 | GEO | 2024/11/21

REPOSITORIES: GEO

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Identify the interplay between N6-methyladenine and gene regulation under hypoxia by randomized empirical model (RNA-seq)

Project description:In this study, we employed RNA-seq to investigate the role of N6-methyladenine (6mA) in chromatin accessibility under hypoxic conditions.

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Identify the interplay between N6-methyladenine and gene regulation under hypoxia by randomized empirical model (ATAC-seq)

Project description:In this study, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to investigate the role of N6-methyladenine (6mA) in chromatin accessibility under hypoxic conditions.

2024-11-21 | GSE260870 | GEO

Identify the interplay between N6-methyladenine and gene regulation under hypoxia by randomized empirical model (6mA)

Project description:This dataset encompasses comprehensive analyses of the epigenetic mark N6-methyladenine (6mA) in human cell lines, focusing on its role under hypoxic conditions and its association with cancer progression. Addressing the challenge of 6mA's low abundance in mammals, we have innovated the 6mA-ChIP-exo-5.1 method. This technique enhances the sensitivity and accuracy of 6mA detection, employing exonuclease-dependent antibody-based approaches combined with whole genome amplification (WGA) to minimize potential noise and false positives.

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Characterization of eukaryotic DNA N6-methyladenine by a highly sensitive restriction enzyme-assisted sequencing

Project description:To interrogate single-base resolution 6mA sites in the genome-wide, we develop DA-6mA-seq (DpnI-Assisted N6-methylAdenine sequencing), an optimized sequencing method taking advantage of restriction enzyme DpnI, which exclusively cleaves methylated adenine sites. We find DpnI also recognizes other sequence motifs besides the canonical GATC restriction sites, largely expanding the application range of this method. DA-6mA-seq requires less starting material and lower sequencing depth than previous methods, but achieves higher sensitivity, providing a good strategy to identify 6mA in large genome with a low abundance of 6mA. We rebuild the 6mA maps of Chlamydomonas by DA-6mA-seq and then apply this method to another two eukaryotic organisms, Plasmodium and Penicillium. Further analysis reveals most 6mA sites are symmetric at various sequence contexts, suggesting 6mA may function as a new heritable epigenetic mark in eukaryotes. A new sequencing method is developed to detect 6mA in eukaryotes

2016-04-12 | E-GEOD-74430 | biostudies-arrayexpress

N6-Methyladenine DNA Modification in Human Genome

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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single-nucleotide resolution sequencing of N6-methyladenine in E. coli genomes and mammalian mitochondrial DNA

Project description:N6-methyladenine (6mA) is a natural DNA modification and functions primarily in restriction-modification (R-M) systems in prokaryotes. Recent studies uncovered the existence and revealed the genome-wide distribution of 6mA in eukaryotes. Specifically, it was reported that 6mA was mainly enriched in mammalian mitochondrial DNA (mtDNA) and could regulate mitochondrial activity. we achieved the genome-wide mapping of 6mA in E. coli genome and mammalian mtDNA at single-nucleotide resolution.

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Characterization of eukaryotic DNA N6-methyladenine by a highly sensitive restriction enzyme-assisted sequencing

2016-04-12 | GSE74430 | GEO

Active N6-Methyladenine demethylation by DMAD regulates gene expression by modulating the binding dynamics of Polycomb protein in neurons

Project description:A Ten-Eleven Translocation (TET) ortholog has been identified as a DNA N6-Methyladenine (6mA) demethylase (DMAD) in Drosophila. However, the molecular roles of 6mA and DMAD remain largely unexplored. Through genome-wide 6mA and transcriptome profiling, we found that 6mA may serve as a repressive epigenetic mark on a group of genes involved in neurodevelopment and neuronal functions. Mechanistically, DMAD coordinates with Trithorax-related complex protein Wds to maintain active transcription by dynamically demethylating intragenic 6mA. Accumulation of 6mA by depleting DMAD recruits Polycomb protein Pc as 6mA reader and contributes to transcriptional repression. Our findings define an epigenetic role for 6mA and suggest that active 6mA demethylation by DMAD plays important roles in fly CNS function by coordinating additional epigenetic mechanisms.

2018-08-02 | GSE67855 | GEO

Stress-induced accumulation of DNA N6-Methyladenine in prefrontal cortex

Project description:Chemical covalent modifications on the 5-carbon position of cytosine, such as 5- methylcytosine and 5-hydroxymethylcytosine, are a set of well-characterized epigenetic marks that shape transcriptional landscaping. Compiling evidence suggests central roles of cytosine modification dynamics in neuronal functions such as memory formation and stress response. N6-methyladenine (6mA) that previously described in bacteria has been recently found in higher eukaryotes, including worms, flies and mice. However, the precise roles and molecular mechanisms of 6mA in mammalian genome, particularly CNS, remain vague. Here we report that the global 6mA level is elevated in mice prefrontal cortex (PFC) upon restraint stress. The 6mA dynamics responding to stress is independent of Tet1 and Tet2 proteins, whose Drosophila ortholog serves as a 6mA demethylase. Genome-wide 6mA profiling in control and stressed PFC reveal that 6mA dynamic changes upon stress predominantly occur on intragenic introns and repetitive elements. Global transcriptome analyzes indicate a set of upregulated genes bearing elevated 6mA levels are highly enriched in neuronal pathways response to stress, suggesting a positive correlation of 6mA with transcription of these loci. In addition, 6mA dynamics in stress response could also influence transposon expression. Furthermore, 6mA is depleted in cortex enhancers, indicating their cis-regulatory roles in transcription. Motif identifications using 6mA dynamic regions provide putative transcription factors and epigenetic modulators binding sites with mechanistic hints. Taken together, our findings reveal dynamic 6mA changes in mice PFC in response to stress, and define its potential epigenetic roles in modulating gene and transposon expression.

2017-10-24 | GSE79543 | GEO

N6-Methyladenine DNA Methylation in Japonica and Indica Rice Genomes and Its Association with Gene Expression, Plant Development, and Stress Responses [BiSulfite-seq]

Project description:N6-Methyladenine (6mA) DNA methylation has recently been implicated as a potential new epigenetic marker in eukaryotes, including the dicot model Arabidopsis thaliana. However, the conservation and divergence of 6mA distribution patterns and functions in plants remain elusive. Here we report high-quality 6mA methylomes at single-nucleotide resolution in rice based on substantially improved genome sequences of two rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica). Analysis of 6mA genomic distribution and its association with transcription suggest that 6mA distribution and function is rather conserved between rice and Arabidopsis. We found that 6mA levels are positively correlated with the expression of key stress-related genes, which may be responsible for the difference in stress tolerance between Nip and 93-11. Moreover, we showed that mutations in DDM1 cause defects in plant growth and decreased 6mA level. Our results reveal that 6mA is a conserved DNA modification that is positively associated with gene expression and contributes to key agronomic traits in plants.

2018-12-10 | GSE121274 | GEO

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