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Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [RNA-seq]

ABSTRACT: Background: DNA N6-methyladenosine (6mA) as a novel epigenetic signaling modification in humans and has been implicated in progression and tumorigenesis of several cancers. However, the function and mechanisms of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Methods: The clinical role of 6mA was investigated by immunohistochemical (IHC) staining and Kaplan-Meier analysis of BC and their normal tissues. 6mA immunoprecipitation (IP) sequencing, mRNA sequencing and bioinformatics analysis were used to screen and validate the direct targets of 6mA. Results: Decreases in N6AMT1 correlated with the extent of 6mA in BC tissues and predicted a worse overall survival of BC patients. Knockdown N6AMT1 markedly reduced 6mA in DNA and promoted the proliferation and migration of BC in vivo and in vitro, whereas overexpression of N6AMT1 had the opposite effect, indicating N6AMT1 is a functional methyltransferase for DNA 6mA and relates with gene transcription. Critical negative regulators of the cell cycle, such as RB1, P21, REST and TP53 were identified as targets of N6AMT1 in BC. Conclusion: These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166576 | GEO | 2022/03/31

REPOSITORIES: GEO

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Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [MeDIP-seq]

Project description:Background: DNA N6-methyladenosine (6mA) as a novel epigenetic signaling modification in humans and has been implicated in progression and tumorigenesis of several cancers. However, the function and mechanisms of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Methods: The clinical role of 6mA was investigated by immunohistochemical (IHC) staining and Kaplan-Meier analysis of BC and their normal tissues. 6mA immunoprecipitation (IP) sequencing, mRNA sequencing and bioinformatics analysis were used to screen and validate the direct targets of 6mA. Results: Decreases in N6AMT1 correlated with the extent of 6mA in BC tissues and predicted a worse overall survival of BC patients. Knockdown N6AMT1 markedly reduced 6mA in DNA and promoted the proliferation and migration of BC in vivo and in vitro, whereas overexpression of N6AMT1 had the opposite effect, indicating N6AMT1 is a functional methyltransferase for DNA 6mA and relates with gene transcription. Critical negative regulators of the cell cycle, such as RB1, P21, REST and TP53 were identified as targets of N6AMT1 in BC. Conclusion: These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.

2022-03-31 | GSE166580 | GEO

Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression

Project description:Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression

| PRJNA701297 | ENA

Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [MeDIP-seq]

Project description:Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [MeDIP-seq]

| PRJNA701301 | ENA

Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [RNA-seq]

Project description:Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [RNA-seq]

| PRJNA701294 | ENA

Abundant DNA 6mA methylation during early embryogenesis of zebrafish

Project description:DNA N6-methyldeoxyadenosine (6mA) is a well known prokaryotic DNA modification and has been shown to exist and play epigenetic roles in eukaryotic DNA. Here we report that 6mA accumulates up to 0.1% of total deoxyadenosine during early embryogenesis of vertebates, but diminishes with progression of the embryo development. During this process most 6mA locates in repetitive regions of the genome.

2016-10-10 | GSE76740 | GEO

Fox Family Protein Jumu Reads 6mA-DNA Codes and Contributes to Zygotic Gene Activation

Project description:N6-methyladenine (6mA) DNA modification in eukaryotic genomes has emerged as a potential epigenetic mark. However, little is known about how 6mA epigenetic codes are read and interpreted in higher eukaryotes. Here we investigate 6mA genome-wide distributions in multiple higher eukaryotes. Using Drosophila as a pioneer system, we show that 6mA exhibits defined patterns and preferentially marks zygotic genes in early embryos. Moreover, we identify that the Fox-family protein, Jumu, is a "6mA-DNA reader" and functions in concert with DMAD to contribute to zygotic gene activation. Further methylome analysis reveals that 6mA modification has common features in genomic DNA from mouse, rat and monkey, and that "forkhead-domain-binding motifs" are enriched in 6mA-marked DNA of these genomes, in a way similar to Drosophila. Collectively, our findings identify the 6mA DNA reader protein and suggest a conserved 6mA-based mechanism in higher eukaryotes.

2023-01-14 | GSE90720 | GEO

6mA-DNA-binding factor Jumu controls maternal-to-zygotic transition upstream of Zelda

Project description:A long-standing question in the field of embryogenesis is how the zygotic genome is precisely activated by maternal factors, allowing normal early embryonic development. We have previously shown that N6-methyladenine (6mA) DNA modification is highly dynamic in early Drosophila embryos and forms an epigenetic mark. However, little is known about how 6mA-formed epigenetic information is decoded. Here we report that the Fox-family protein Jumu binds 6mA-marked DNA and acts as a maternal factor to regulate the maternal-to-zygotic transition. We find that zelda encoding the pioneer factor Zelda is marked by 6mA. Our genetic assays suggest that Jumu controls the proper zygotic genome activation (ZGA) in early embryos, at least in part, by regulating zelda expression. Thus, our findings not only support that the 6mA-formed epigenetic can be read by specific transcription factors, but also uncover a mechanism by which the Jumu regulates ZGA partially through Zelda in early embryos.

2019-04-18 | GSE86795 | GEO

Risk of T1D progression in islet autoantibody positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function

Project description:To identify genes with expression levels that are associated with T1D progression from AbP (islet autoantibody positive), global gene expression changes were analyzed in AbP subjects with different T1D progression rate. Total RNA were obtained from peripheral blood mononuclear cells (PBMC) of total 36 AbP subjects with different T1D progression rate. Microarray was carried out to analyze gene expression and Kaplan-Meier survival analysis and log-rank test were used to compare differences in diabetes-free survival between groups classified based on single gene expression.

2014-04-10 | E-GEOD-51058 | biostudies-arrayexpress

Genome wide 6mA modification change upon mitochondial stress in C.elegans

Project description:We discovered 364 peaks enrichment change in wild-type C.elegans genome by 6mA MeDIP-seq, which indicated those genes response to mitochondrial stress and may function in mitochondrial stress response.

2018-09-27 | GSE118268 | GEO

N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

Project description:N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms. Multiple sequencing methods are developed to profile the distribution of 6mA in Chlamydomonas including MeDIP-Seq, enzyme-treated DNA-Seq, MNase-Seq and RNA-Seq.

2015-04-30 | E-GEOD-62690 | biostudies-arrayexpress

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