{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/001/SRR2154861/SRR2154861_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/007/SRR2154867/SRR2154867_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/002/SRR2154862/SRR2154862_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/004/SRR2154864/SRR2154864_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/000/SRR2154860/SRR2154860_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/006/SRR2154866/SRR2154866_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/005/SRR2154865/SRR2154865_subreads.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/003/SRR2154863/SRR2154863_subreads.fastq.gz"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Andrew Xiao, Genetics, Yale Stem Cell Center"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA292545"],"scientific_name":["Mus musculus"],"tag":["xref:PubMed:27027282"],"long_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 a native-ChIP approach to enrich for DNA molecules residing in H2A.X-deposition regions in mouse ESCs as previously described. Then, co-purified DNA molecules from WT or KO ESCs were subject to SMRT sequencing and data analysis for DNA modifications (Pacific Biosciences). Overall design: H2A.X Native ChIP coupling with SMRT sequencing (separate the short \"S\" and long \"L\" part to sequencing)"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Mus musculus","description":"H2A.X SMRT-ChIP","dates":{"last_updated":"2025-09-24","first_public":"2016-10-10"},"accession":"PRJNA292545","cross_references":{"GEO":["GSE71940"],"taxon":["10090"],"PubMed":["27027282"]}}