NIG_MoG: a mouse genome navigator for exploring intersubspecific genetic polymorphisms

Takada, Toyoyuki; Yoshiki, Atsushi; Obata, Yuichi; Yamazaki, Yukiko; Shiroishi, Toshihiko

doi:10.1007/s00335-015-9569-8

Cited by 15 publications

(14 citation statements)

References 18 publications

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“…All experiments using animals were performed under the ethical guidelines of Kyoto University, University of Tokyo, and Kumamoto University. MSM/Ms were obtained from RIKEN Bio Resource Center (Takada et al., 2013, Takada et al., 2015).…”

Section: Methodsmentioning

confidence: 99%

De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency

et al. 2019

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Summary CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, was often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs.

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Section: Methodsmentioning

confidence: 99%

De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency

et al. 2019

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“…All animal studies were conducted in compliance with ethical regulations in The University of Tokyo and Kyoto University and were approved by Institute of Medical Sciences, The University of Tokyo and Center for iPS Cell Research and Application (CiRA), Kyoto University. MSM/Ms were obtained from RIKEN Bio Resource Center 34,35 . B6;129S4-Dnmt3a < tm1Enl> mice 5 were obtained from RIKEN Bio Resource Center.…”

Section: Methodsmentioning

confidence: 99%

Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development

et al. 2020

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De novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.

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“…Gene-specific primers (Supplementary Table 1) were designed using Primer3 52 and Primer-BLAST 53 . The primers were checked to avoid mismatching against the MSM genome or transcripts using the NIG Mouse Genome Database (NIG_MoG) 54 . The mRNA levels were compared more than three times for each test.…”

Section: Methodsmentioning

confidence: 99%

“…This variant information was recalibrated by the VariantRecalibrator/ApplyRecalibration commands by GATK with mode SNP and INDEL, respectively. In some wild-derived strains (BFM/2, PGN2, HMI, KJR, SWN, CHD, NJL, BGL2, MSM, and JF1), the SNP data were obtained using the VariantTable function in the NIG Mouse Genome Database (NIG_MoG2) 54 . Applying only the homologous SNP variants, FASTA sequences for each strain were constructed by the FastaAlternateReferenceMaker command using GATK, in which repetitive sequences were excluded based on UCSC’s RepeatMasker information.…”

Section: Methodsmentioning

confidence: 99%

Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation

2019

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Black coat color (nonagouti) is a widespread classical mutation in laboratory mouse strains. The intronic insertion of endogenous retrovirus VL30 in the nonagouti ( a ) allele of agouti gene was previously reported as the cause of the nonagouti phenotype. Here, we report agouti mouse strains from East Asia that carry the VL30 insertion, indicating that VL30 alone does not cause the nonagouti phenotype. We find that a rare type of endogenous retrovirus, β4, was integrated into the VL30 region at the a allele through nested retrotransposition, causing abnormal splicing. Targeted complete deletion of the β4 element restores agouti gene expression and agouti coat color, whereas deletion of β4 except for a single long terminal repeat results in black-and-tan coat color. Phylogenetic analyses show that the a allele and the β4 retrovirus originated from an East Asian mouse lineage most likely related to Japanese fancy mice. These findings reveal the causal mechanism and historic origin of the classical nonagouti mutation.

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NIG_MoG: a mouse genome navigator for exploring intersubspecific genetic polymorphisms

Cited by 15 publications

References 18 publications

De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency

De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency

Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development

Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation

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