METTL4-mediated N6-methyladenine DNA modification regulates thermotolerance in Arabidopsis thaliana
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE237262 | GEO | 2023/11/20
REPOSITORIES: GEO
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Project description:METTL4-mediated N6-methyladenine DNA modification regulates thermotolerance in Arabidopsis thaliana
| PRJNA994492 | ENA
Project description:DNA methylation has a role in the pathogenesis of essential hypertension. DNA N6-methyladenine (6mA) modification as a novel adenine methylation exists in human tissues, but whether it plays a role in hypertension development remains unclear. Here, we reported that the global 6mA DNA level in leukocytes was significantly reduced in patients with hypertension and was reversed with successful treatment. Age, systolic blood pressure, and serum total cholesterol and high-density lipoprotein levels were associated with decreased leukocyte 6mA DNA level. Elevated ALKBH1 (AlkB homolog 1), a demethylase of 6mA, level mediated this dynamic change in 6mA level in leukocytes and vascular smooth muscle cells in hypertension mouse and rat models. Knockdown of ALKBH1 suppressed angiotensin II-induced vascular smooth muscle phenotype transformation, proliferation and migration. ALKBH1-6mA directly and negatively regulated hypoxia inducible factor 1 ? (HIF1?), which responded to angiotensin II-induced vascular remodeling. Collectively, our results demonstrate a potential epigenetic role for ALKBH1-6mA regulation in hypertension development, diagnosis and treatment.
| S-EPMC7185115 | biostudies-literature
Project description:DNA N6-methyladenine (6mA) modifications expand the information capacity of DNA and have long been known to exist in bacterial genomes. Xanthomonas oryzae pv. Oryzicola (Xoc) is the causative agent of bacterial leaf streak, an emerging and destructive disease in rice worldwide. However, the genome-wide distribution patterns and potential functions of 6mA in Xoc are largely unknown. In this study, we analyzed the levels and global distribution patterns of 6mA modification in genomic DNA of seven Xoc strains (BLS256, BLS279, CFBP2286, CFBP7331, CFBP7341, L8 and RS105). The 6mA modification was found to be widely distributed across the seven Xoc genomes, accounting for percent of 3.80, 3.10, 3.70, 4.20, 3.40, 2.10, and 3.10 of the total adenines in BLS256, BLS279, CFBP2286, CFBP7331, CFBP7341, L8, and RS105, respectively. Notably, more than 82% of 6mA sites were located within gene bodies in all seven strains. Two specific motifs for 6 mA modification, ARGT and AVCG, were prevalent in all seven strains. Comparison of putative DNA methylation motifs from the seven strains reveals that Xoc have a specific DNA methylation system. Furthermore, the 6 mA modification of rpfC dramatically decreased during Xoc infection indicates the important role for Xoc adaption to environment.
| S-EPMC6215013 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-01 | GSE118093 | GEO
Project description:N6-Methyladenine (N6-mA or 6 mA) is an epigenetic DNA modification in eukaryotic genomes. In contrast to the well-established roles of 5-methylcytosine for epigenetic regulation of gene expression, the functional roles of N6-mA remain elusive. In particular, the impact of N6-mA modification of the DNA template on RNA polymerase II (pol II) transcription elongation is not known. In this work, using the Saccharomyces cerevisiae pol II transcriptional elongation system as a model, we investigated the molecular mechanism of pol II recognition and processing of N6-mA sites via both biochemical and structural approaches. We found that N6-mA causes site-specific pol II pausing/stalling. Structural analysis revealed that while N6-mA can reach the +1 template position, the stability of the N6-mA and UTP base pairing is compromised. Taken together, we reveal that the presence of the 6-methyl group on adenine reduces incorporation efficiency and promotes backtracking translocation. Our studies with yeast pol II provide molecular insights into understanding the impacts of N6-mA on pol II transcription dynamics in different organisms.
| S-EPMC5812728 | biostudies-literature
Project description:Triple negative breast cancer (TNBC) is a subtype of breast cancer with strong aggressiveness and poor clinical treatment effect, accounting for about 10-20% of breast cancer cases. N(6)-methyldeoxyadenosine (6mA) is the most conservative DNA modification in prokaryotes and eukaryotes. It is widely found in bacteria and has such functions as DNA mismatch repair, chromosome separation and virulence regulation. We determined that 6mA was modified in TNBC cell line MDA-MB-231 and the TNBC tissue. Meanwhile, compared with normal tissues, the expression level of 6mA and its methylase N6AMT1 was significantly decreased in TNBC tissue. MDA-MB-231cells were cultured with 8μM Olaparib for 2 months to construct drug-resistant cell line 231-RO. It was found that the level of 6mA also increased significantly, and the expression of N6AMT1 or ALKBH1 could effectively influence the drug resistance. Subsequently, we found that LINP1 was highly expressed in 231-RO, which was involved in DNA repair, and the expression of LINP1 could be positively regulated by 6mA modification. LINP1 expression level is directly related to TNBC drug resistance. The above results indicate that 6mA may be a new biological marker of TNBC. Meanwhile, 6mA modification may be involved in the regulation of Olaparib resistance.
| S-EPMC7887291 | biostudies-literature
Project description:N6-methyladenine modification (m6dA) has recently been identified in eukaryote genomic DNA. The methylation destabilizes the duplex structure when the adenine forms a Watson-Crick base pair, whereas the methylation on a terminal unpaired adenine stabilizes the duplex structure by increasing the stacking interaction. In this study, the effects of m6dA modification on the thermal stability of four distinct telomeric G-quadruplex (G4) structures were investigated. The m6dA-modified telomeric oligonucleotide d[AGGG(TTAGGG)3] that forms a basket-type G4 in Na+, d[(TTAGGG)4TT] that forms a hybrid-type G4 in K+ (Form-2), d[AAAGGG(TTAGGG)3AA] that forms a hybrid-type G4 in K+ (Form-1), and d[GGG(TTAGGG)3T] that forms a basket-type G4 with two G-tetrads in K+ (Form-3) were analyzed. Circular dichroism melting analysis demonstrated that (1) A7- and A19-methylation destabilized the basket-type G4 structure that formed in Na+, whereas A13-methylation stabilized the structure; (2) A15-methylation stabilized the Form-2 G4 structure; (3) A15- and A21-methylations stabilized the Form-1 G4 structure; and (4) A12-methylation stabilized the Form-3 G4 structure. These results suggest that m6dA modifications may affect the thermal stability of human telomeric G4 structures in regulating the biological functions.
| S-EPMC8594671 | biostudies-literature
Project description:Eukaryotic DNA methylation has been receiving increasing attention for its crucial epigenetic regulatory function. The recently developed single-molecule real-time (SMRT) sequencing technology provides an efficient way to detect DNA N6-methyladenine (6mA) and N4-methylcytosine (4mC) modifications at a single-nucleotide resolution. The family Rosaceae contains horticultural plants with a wide range of economic importance. However, little is currently known regarding the genome-wide distribution patterns and functions of 6mA and 4mC modifications in the Rosaceae. In this study, we present an integrated DNA 6mA and 4mC modification database for the Rosaceae (MDR, http://mdr.xieslab.org). MDR, the first repository for displaying and storing DNA 6mA and 4mC methylomes from SMRT sequencing data sets for Rosaceae, includes meta and statistical information, methylation densities, Gene Ontology enrichment analyses, and genome search and browse for methylated sites in NCBI. MDR provides important information regarding DNA 6mA and 4mC methylation and may help users better understand epigenetic modifications in the family Rosaceae.
| S-EPMC6572862 | biostudies-literature
Project description:Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis. Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions. Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis. Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.
| S-EPMC9908960 | biostudies-literature
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.
2017-10-02 | GSE104475 | GEO