ALKBH1-mediated DNA N6-methyladenine Modification Regulates H3K9me3-dependent Heterochromatin in Neural Tube Development
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ABSTRACT:
PROVIDER: PRJNA1118217 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29234645_1.fastq.gz | Fastqsanger.gz | |||
| SRR29234645_2.fastq.gz | Fastqsanger.gz | |||
| SRR29234646_1.fastq.gz | Fastqsanger.gz | |||
| SRR29234646_2.fastq.gz | Fastqsanger.gz | |||
| SRR29234647_1.fastq.gz | Fastqsanger.gz |
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Project description:Neural Tube Defects (NTDs) are a class of severe congenital developmental defects caused by abnormal closure of the neural tube during early embryonic development, including conditions such as anencephaly, spina bifida, and encephalocele. Currently, NTDs are considered to result from the combined effects of genetic and environmental factors, particularly maternal folate intake during pregnancy, leading to widespread epigenetic dysregulation. However, the role of N6-methyladenine (N6-mA) in embryonic neural development remains largely unknown. Here, we found significant upregulation of Alkbh1 and concomitant significant downregulation of overall 6mA in brain tissue of a mouse model of NTDs. Further investigation through MeDIP, CUT&TAG, and single-cell sequencing revealed crosstalk between N6-mA and H3K9me3-marked heterochromatin, primarily impacting the involvement of embryonic glial cells in the formation of the hindbrain during embryonic neural tube development. These findings collectively suggest a potential epigenetic role of N6-mA in mammalian brain development, potentially exhibiting cell type specificity.
2025-05-01 | GSE268661 | GEO
Project description:Neural Tube Defects (NTDs) are a class of severe congenital developmental defects caused by abnormal closure of the neural tube during early embryonic development, including conditions such as anencephaly, spina bifida, and encephalocele. Currently, NTDs are considered to result from the combined effects of genetic and environmental factors, particularly maternal folate intake during pregnancy, leading to widespread epigenetic dysregulation. However, the role of N6-methyladenine (N6-mA) in embryonic neural development remains largely unknown. Here, we found significant upregulation of Alkbh1 and concomitant significant downregulation of overall 6mA in brain tissue of a mouse model of NTDs. Further investigation through MeDIP, CUT&TAG, and single-cell sequencing revealed crosstalk between N6-mA and H3K9me3-marked heterochromatin, primarily impacting the involvement of embryonic glial cells in the formation of the hindbrain during embryonic neural tube development. These findings collectively suggest a potential epigenetic role of N6-mA in mammalian brain development, potentially exhibiting cell type specificity.
2024-11-28 | GSE268545 | GEO
Project description:Neural Tube Defects (NTDs) are a class of severe congenital developmental defects caused by abnormal closure of the neural tube during early embryonic development, including conditions such as anencephaly, spina bifida, and encephalocele. Currently, NTDs are considered to result from the combined effects of genetic and environmental factors, particularly maternal folate intake during pregnancy, leading to widespread epigenetic dysregulation. However, the role of N6-methyladenine (N6-mA) in embryonic neural development remains largely unknown. Here, we found significant upregulation of Alkbh1 and concomitant significant downregulation of overall 6mA in brain tissue of a mouse model of NTDs. Further investigation through RNA-seq，MeDIP, CUT&TAG, and single-cell sequencing revealed crosstalk between N6-mA and H3K9me3-marked heterochromatin, primarily impacting the involvement of embryonic glial cells in the formation of the hindbrain during embryonic neural tube development. These findings collectively suggest a potential epigenetic role of N6-mA in mammalian brain development, potentially exhibiting cell type specificity.
2025-05-01 | GSE268764 | GEO
Project description:Neural Tube Defects (NTDs) are a class of severe congenital developmental defects caused by abnormal closure of the neural tube during early embryonic development, including conditions such as anencephaly, spina bifida, and encephalocele. Currently, NTDs are considered to result from the combined effects of genetic and environmental factors, particularly maternal folate intake during pregnancy, leading to widespread epigenetic dysregulation. However, the role of N6-methyladenine (N6-mA) in embryonic neural development remains largely unknown. Here, we found significant upregulation of Alkbh1 and concomitant significant downregulation of overall 6mA in brain tissue of a mouse model of NTDs. Further investigation through RNA-seq，MeDIP, CUT&TAG, and single-cell sequencing revealed crosstalk between N6-mA and H3K9me3-marked heterochromatin, primarily impacting the involvement of embryonic glial cells in the formation of the hindbrain during embryonic neural tube development. These findings collectively suggest a potential epigenetic role of N6-mA in mammalian brain development, potentially exhibiting cell type specificity.
2025-05-01 | GSE268763 | GEO
Project description:ALKBH1-mediated DNA N6-methyladenine Modification Regulates H3K9me3-dependent Heterochromatin in Neural Tube Development [scRNA-Seq]
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Project description:ALKBH1-mediated DNA N6-methyladenine Modification Regulates H3K9me3-dependent Heterochromatin in Neural Tube Development [Cut & Tag]
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Project description:ALKBH1-mediated DNA N6-methyladenine Modification Regulates H3K9me3-dependent Heterochromatin in Neural Tube Development [RNA-Seq]
| PRJNA1118704 | ENA
Project description:It has widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes, whereas the other forms, such as N6-methyladenine, primarily exist in prokaryotes and only a few eukaryotes. Herein, we demonstrated the surprising presence of N6-methyladenine in mammalian genomes, especially, mouse embryonic stem cells. This modification is enriched at histone variant H2A.X-deposited genomic regions in wild type embryonic stem cells. Our work also showed that a previously unknown DNA demethylase, Alkbh1, is the major demethylase for N6-methyladenine in embryonic stem cells. Increase of N6-methyladenine levels in Alkbh1 deficient cells leads to silencing of genes that regulate embryonic development. Surprisingly, genes located on the X-chromosome, but not the Y-chromosome or autosomes are preferentially silenced by N6-methyladenine. Strikingly, N6-methyladenine in Alkbh1 deficient cells are specifically deposition at young, full-length subfamilies of LINE1 transposons that are strongly enriched on the X chromosome. Furthermore, N6-methyladenine deposition on LINE1s pattern is inversely correlated with their evolutionary age. The deposition of N6-methyladenine results in epigenetic silencing of such L1s, which are otherwise actively transcribed in wild type embryonic stem cells, and the neighboring enhancers and genes. Furthermore, N6-methyladenine induced-silencing resists gene activation signals during embryonic stem cell differentiation. Thus, N6-methyladenine adopts a new function in epigenetic silencing in evolution, distinct from its role in gene activation in other organisms. In summary, our results demonstrate that N6-methyladenine unexpectedly constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes. RNASeq compare the differential expressed genes in Alkbh1 KO and WT ES cell total RNA with mRNA HiSeq sequencing
2016-03-30 | E-GEOD-71943 | biostudies-arrayexpress
Project description:It has widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes, whereas the other forms, such as N6-methyladenine, primarily exist in prokaryotes and only a few eukaryotes. Herein, we demonstrated the surprising presence of N6-methyladenine in mammalian genomes, especially, mouse embryonic stem cells. This modification is enriched at histone variant H2A.X-deposited genomic regions in wild type embryonic stem cells. Our work also showed that a previously unknown DNA demethylase, Alkbh1, is the major demethylase for N6-methyladenine in embryonic stem cells. Increase of N6-methyladenine levels in Alkbh1 deficient cells leads to silencing of genes that regulate embryonic development. Surprisingly, genes located on the X-chromosome, but not the Y-chromosome or autosomes are preferentially silenced by N6-methyladenine. Strikingly, N6-methyladenine in Alkbh1 deficient cells are specifically deposition at young, full-length subfamilies of LINE1 transposons that are strongly enriched on the X chromosome. Furthermore, N6-methyladenine deposition on LINE1s pattern is inversely correlated with their evolutionary age. The deposition of N6-methyladenine results in epigenetic silencing of such L1s, which are otherwise actively transcribed in wild type embryonic stem cells, and the neighboring enhancers and genes. Furthermore, N6-methyladenine induced-silencing resists gene activation signals during embryonic stem cell differentiation. Thus, N6-methyladenine adopts a new function in epigenetic silencing in evolution, distinct from its role in gene activation in other organisms. In summary, our results demonstrate that N6-methyladenine unexpectedly constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes. First, we used different histone antibodies to enrich for DNA molecules with histone modification or specific variant in mouse ESCs as previously described Native-ChIP methods. Then, co-purified DNA molecules from WT or KO ESCs were subject to HiSeq2000 sequencing and data analysis for histone modification or variant peaks. Native ChIP coupling with HiSeq sequencing
2016-03-30 | E-GEOD-71942 | biostudies-arrayexpress
Project description:Genetic drivers of cancer can be dysregulated through epigenetic modifications of DNA. While the critical role of DNA 5-methylcytosine (5mC) in the regulation of transcription is recognized, the functions of other non-canonical DNA modifications remain obsure. Here, we report the identification of novel N(6)-methyladenine (N6-mA) DNA modifications in human tissues and implicate this epigenetic regulation in human disease, the highly malignant brain cancer, glioblastoma. Glioblastoma upregulates N6-mA levels, which co-localize with heterochromatic histone modifications, namely H3K9me3. N6-mA levels are dynamically regulated by the DNA demethylase, ALKBH1, to transcriptionally silence oncogenic pathways through decreasing chromatin accessibility. Targeting the N6-mA regulator, ALKBH1, in patient-derived human glioblastoma models inhibited tumor cell proliferation and extended survival of tumor-bearing mice, supporting this novel DNA modification as a potential new molecular therapeutic target for glioblastoma. Collectively, our results uncover a novel epigenetic node in cancer through the DNA modification, N6-mA.
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