Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene

Miyazaki, Kazumi; Mapendano, Christophe K.; Fuchigami, Tomokazu; Kondo, Shinji; Ohta, Tohru; Kinoshita, Akira; Tsukamoto, Kazuhiro; Yoshiura, Ko–ichiro; Niikawa, Norio; Kishino, Tatsuya

doi:10.1016/j.gene.2008.11.019

Cited by 14 publications

(14 citation statements)

References 20 publications

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“…The reduction in the global percentage of methylated CpGs in 4C neurons is specific for the Peg3 imprinted region as the Snrpn imprinting domain-controlling DMR (SCD) ( 8 , 28 ), also known to regulate a genomic domain (Figure 1B ) comprising genes with neuronal expression ( 10 ), showed similar levels of global methylation in both 2C and 4C cortical neurons (Figure 3E ). This conclusion was further supported by the analysis with specific primers (Figure 2 ) of individual CpGs within the SCD, either by pyrosequencing (Figure 3F ) or Sanger sequencing ( Supplementary Figure S2B ).…”

Section: Resultsmentioning

confidence: 95%

Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting

Patiño-Parrado

Gómez-Jiménez

López-Sánchez

et al. 2017

Nucleic Acids Research

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Imprinted genes are regulated by allele-specific differentially DNA-methylated regions (DMRs). Epigenetic methylation of the CpGs constituting these DMRs is established in the germline, resulting in a 5-methylcytosine-specific pattern that is tightly maintained in somatic tissues. Here, we show a novel epigenetic mark, characterized by strand-specific hemimethylation of contiguous CpG sites affecting the germline DMR of the murine Peg3, but not Snrpn, imprinted domain. This modification is enriched in tetraploid cortical neurons, a cell type where evidence for a small proportion of formylmethylated CpG sites within the Peg3-controlling DMR is also provided. Single nucleotide polymorphism (SNP)-based transcriptional analysis indicated that these epigenetic modifications participate in the maintainance of the monoallelic expression pattern of the Peg3 imprinted gene. Our results unexpectedly demonstrate that the methylation pattern observed in DMRs controlling defined imprinting regions can be modified in somatic cells, resulting in a novel epigenetic modification that gives rise to strand-specific hemimethylated domains functional for genomic imprinting. We anticipate the existence of a novel molecular mechanism regulating the transition from fully methylated CpGs to strand-specific hemimethylated CpGs.

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Section: Resultsmentioning

confidence: 95%

Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting

Patiño-Parrado

Gómez-Jiménez

López-Sánchez

et al. 2017

Nucleic Acids Research

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“…The data from human and mouse models point to SNURF's being a protein that is produced along with SmN from a bicistronic transcript (this phenomenon is rarely observed in eukaryotes), with each cistron potentially playing a role in the disease [ 79 , 80 ]. The highly conserved activator sequence in Snrpn intron 1 demonstrates developmental dynamic changes of DNA methylation and has a methylation-sensitive enhancer activity in rodents; thereby it may control tissue-specific expression of transcripts [ 81 ]. Note, that the ubiquitously expressed transcription factor 1, Sp1, interacts with the SNURF protein, according to the Biological General Repository for Interaction Datasets, BioGRID [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

et al. 2014

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BackgroundEtiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats.ResultsFirst, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-β signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may contribute to the development of cataract and retinopathy.ConclusionsThis study is the first RNA-Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing read depth. The integration of QTL and transcriptomic analyses in our study forms the basis of future research into the relationship between the candidate genes within the congenic regions and specific changes in the retinal transcriptome as possible causal mechanisms that underlie age-associated disorders.

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“…Some of the genes showing strongest AIE differences between the A and B subgroups are known to be imprinted and likely contribute to the parental effect of NIC SA. For instance, Snrpn, a known paternally expressed gene 47,48 , and its bicistronic transcript partner Snurf, play an important role in adult neurogenesis 69 that is relevant to both NIC SST and SA (Figure 6f, g). Snrpn and Snurf are regulated via a paternal imprinting locus 70 and its dysregulation is associated with Praeder-Willi Syndrome 71 and inability to regenerate axons 72 .…”

Section: Discussionmentioning

confidence: 99%

“…8d, Supplementary Table 10). Many of these SNPs were found in genes or regions known to be imprinted in rodents or humans (Supplementary Table 10); for instance, small nuclear ribonucleoprotein-associated polypeptide N (Snrpn) 47,48 , ubiquitin-protein ligase E3A (Ube3a) 49 , and Trappc9 50 . AIE of Snrpn showed a strong bias toward the paternal allele of the SAinclined subgroup B; correspondingly, Snrpn showed significant DE downregulation in the VTA (Figure 7a, b, Supplementary Table 10).…”

Section: Parental Effect Of Sa Is Associated With Allelic Imbalance Omentioning

confidence: 99%

Transcriptomic signatures of sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes

Kozlova

Butler

Zhang

et al. 2020

Preprint

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Rodents are frequently used to model drug addiction, yet their genetic relevance to human addictive behaviors especially the mounting genome-wide association study (GWAS) findings is poorly understood. Considering a possible gateway drug role of nicotine (NIC), we modeled NIC addiction, specifically NIC sensitization (SST) and self-administration (SA), in F1 progeny of inbred Envigo rats (F344/BN) and conducted integrative genomics analyses. We unexpectedly observed male-specific NIC SST and a parental effect of SA only present in paternal F344 crosses. Transcriptional profiling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) core and shell further revealed sex and brain region-specific transcriptomic signatures of SST and SA. We found that genes associated with SST and SA were enriched for those related to synaptic processes, myelin sheath, and tobacco use disorder or chemdependency. Interestingly, SST-associated genes were often downregulated in male VTA but upregulated in female VTA, and strongly enriched for smoking GWAS risk variants, possibly explaining the male-specific SST. For SA, we found widespread region-specific allelic imbalance of expression (AIE), of which genes showing AIE bias towards paternal F344 alleles in NAc core were strongly enriched for SA-associated genes and for GWAS risk variants of smoking initiation, likely contributing to the parental effect of SA. The transcriptional signatures of sex-specific nicotine SST and SA suggest a mechanistic link between genes underlying these processes and human nicotine addiction, providing a resource for understanding the biology underlying the GWAS findings on human smoking and other addictive phenotypes.

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Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene

Cited by 14 publications

References 20 publications

Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting

Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

Transcriptomic signatures of sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes

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