The effect of paternal haploinsufficiency for Dnmt3L
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE7384 | GEO | 2007/03/29
SECONDARY ACCESSION(S): PRJNA97863
REPOSITORIES: GEO
Similar Datasets
Project description:There is increasing evidence that epigenetic information can be inherited across generations in mammals, despite extensive reprogramming both in the gametes and the early developing embryo. One corollary to this is that disruption of the establishment of epigenetic state in the gametes of a parent, as a result of heterozygosity for mutations in genes involved in reprogramming, could affect the phenotype of offspring that do not inherit the mutant allele. Here we show that such effects do occur following paternal inheritance in the mouse. We detect changes to transcription and chromosome ploidy in adult animals. Paternal effects of this type have not been reported previously in mammals and suggest that the untransmitted genotype of male parents can influence the phenotype of their offspring. Experiment Overall Design: Offspring of Dnmt3L+/- sires compared to offspring of Dnmt3L+/+ sires
2008-06-15 | E-GEOD-7384 | biostudies-arrayexpress
Project description:During oogenesis, DNA methyltransferase 3-like (Dnmt3l) is required for the establishment of the maternal germline DNA methylation imprints that in the offspring, govern the parent-of-origin-specific expression of most known imprinted genes (Science 2001, 294:2536-9). Dnmt3l-deficient dams were crossed with wildtype sires to obtain Dnmt3l-/+ embryos that lack maternal methylation imprints. Gene expression was measured in Dnmt3l-/+ and wildtype embryos and is expected to differ for imprinted genes that are under the control of a maternal methylation mark. Keywords: genetic modification, DNA methylation
2008-04-14 | GSE8756 | GEO
Project description:During oogenesis, DNA methyltransferase 3-like (Dnmt3l) is required for the establishment of the maternal germline DNA methylation imprints that in the offspring, govern the parent-of-origin-specific expression of most known imprinted genes (Science 2001, 294:2536-9). Dnmt3l-deficient dams were crossed with wildtype sires to obtain Dnmt3l-/+ embryos that lack maternal methylation imprints. Gene expression was measured in Dnmt3l-/+ and wildtype embryos and is expected to differ for imprinted genes that are under the control of a maternal methylation mark. Experiment Overall Design: 1 normal control sample/array. 2 biologically replicate Dnmt3l-/+ samples/arrays.
2008-06-16 | E-GEOD-8756 | biostudies-arrayexpress
Project description:During early mammalian development, DNA methylation undergoes two waves of reprogramming, enabling transitions between somatic cells, oocyte and embryo. The first wave of de novo DNA methylation establishment occurs in the oocytes. Its molecular mechanisms has been studied in mouse, a classical mammalian model. Current dogma describes DNA methyltransferase 3A (DNMT3A) and its cofactor DNMT3L as two essential factors for oocyte DNA methylation – the ablation of either leads to nearly complete abrogation of DNA methylation. However, DNMT3L is not expressed in human oocytes, suggesting that the mechanism uncovered in mouse is not universal across mammals. We analyzed available RNA-seq datasets from oocytes of multiple mammals including our novel naked mole-rat oocytes dataset, and revealed that Dnmt3l is expressed only in the oocytes of mouse, rat and golden hamster. We identified a specific promoter sequence recognised by an oocyte transcription factor complex associated with Dnmt3l activity and demonstrated that it emerged in the rodent clade Eumuroida, comprising the families Muridae (mice, rats, gerbils) and Cricetidae (hamsters). Therefore, Dnmt3l is expressed and consequently plays a role in de novo DNA methylation only in the oocytes of these species, instead of being an essential pan-mammalian factor.
2023-11-13 | GSE236457 | GEO
Project description:We found that Dnmt3l-KO donor cells display decreased levels of H3K9me3 and H3K27me3 accumulation, higher level of active histone mark H3K27ac and increased cytoplasmic localization of HDAC1, implicating a permissive epigenetic state beneficial for nuclear reprogramming. To investigate the gene expression profiles of MEFs and to find out the potential genes responsible for the improvement of Dnmt3l-KO cloned embryos.
2015-08-01 | E-GEOD-69007 | biostudies-arrayexpress
Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny. 2 sires of advanced paternal age (12-16 months of age) and 2 control (3 months of age) sires were mated to dams (3 months of age) to create 6 offspring of advanced paternal age (APA) and 6 control offspring (C), respectively, with an even number of sexes within each group of offspring. A commerical aCGH and a custom CNV array (both supplied by Agilent) were used in combination to detect copy number variations in the genomes of the offspring and their parents. DNA from all male animals was hybridized against a male reference animal and that from all female animals against a female reference animal.
2011-07-12 | E-GEOD-29454 | biostudies-arrayexpress
Project description:The offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. It has been proposed that de novo point mutations and copy number variants (CNVs) in the continually dividing spermatogonia underlie this association. In light of the evidence implicating CNVs with schizophrenia and autism, here we use a mouse model to test the hypothesis that the offspring of older males have an increased risk of de novo CNVs. Three-month-old and fourteen- to sixteen-month-old C57BL/6J sires were mated with three-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, seven distinct CNVs were identified in a discovery set of twelve offspring and their parents. Competitive quantitative PCR was employed to confirm the variants and establish their frequency in a replication set of 77 offspring and their parents. Six de novo CNVs were detected in the offspring of older sires, while none were detected in the control group. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. Two of the CNVs were associated with behavioural and/or neuroanatomical phenotypic features. This is the first experimental demonstration that the offspring of older males have more de novo CNVs. The results suggest that offspring of older fathers may be at increased risk of neurodevelopmental disorders such as schizophrenia and autism via the generation of de novo CNV in the male germline. In light of the trends for delayed parenthood in many societies, and in light of the potential for these CNVs to accumulate over subsequent generations, the impact of these mechanisms on the health of future generations warrants closer scrutiny. 2 sires of advanced paternal age (12-16 months of age) and 2 control (3 months of age) sires were mated to dams (3 months of age) to create 6 offspring of advanced paternal age (APA) and 6 control offspring (C), respectively, with an even number of sexes within each group of offspring. A commerical aCGH and a custom CNV array (both supplied by Agilent) were used in combination to detect copy number variations in the genomes of the offspring and their parents. DNA from all male animals was hybridized against a male reference animal and that from all female animals against a female reference animal.
2011-07-12 | E-GEOD-29455 | biostudies-arrayexpress
Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males
2022-04-01 | GSE199661 | GEO
Project description:Background: Following cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation. Methods: We studied the intergenerational influence of neonatal cardiac injury in the mouse. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult. Results: We show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy. Conclusions: The memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.
2024-11-08 | GSE254827 | GEO
Project description:We found that Dnmt3l-KO donor cells display decreased levels of H3K9me3 and H3K27me3 accumulation, higher level of active histone mark H3K27ac and increased cytoplasmic localization of HDAC1, implicating a permissive epigenetic state beneficial for nuclear reprogramming.
2015-08-01 | GSE69007 | GEO