Expression analysis suggests that DNMT3L is required for oocyte de novo DNA methylation only in Muridae and Cricetidae rodents
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ABSTRACT:
PROVIDER: PRJNA990944 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25119978_1.fastq.gz | Fastqsanger.gz | |||
| SRR25119978_2.fastq.gz | Fastqsanger.gz | |||
| SRR25679462_1.fastq.gz | Fastqsanger.gz | |||
| SRR25679462_2.fastq.gz | Fastqsanger.gz | |||
| SRR25679463_1.fastq.gz | Fastqsanger.gz |
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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:BackgroundDuring 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 oocytes. Its molecular mechanisms have been studied in mouse, a classical mammalian model. Current model 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.ResultsWe analysed available RNA-seq data sets from oocytes of multiple mammals, including our novel data sets of several rodent species, and revealed that Dnmt3l is expressed only in the oocytes of mouse, rat and golden hamster, and at a low level in guinea pigs. We identified a specific promoter sequence recognised by an oocyte transcription factor complex associated with strong Dnmt3l activity and demonstrated that it emerged in the rodent clade Eumuroida, comprising the families Muridae (mice, rats, gerbils) and Cricetidae (hamsters). In addition, an evolutionarily novel promoter emerged in the guinea pig, driving weak Dnmt3l expression, likely without functional relevance. Therefore, Dnmt3l is expressed and consequently plays a role in oocyte de novo DNA methylation only in a small number of rodent species, instead of being an essential pan-mammalian factor. In contrast to somatic cells, where catalytically inactive DNMT3B interacts with DNMT3A, forming a heterotetramer, we did not find evidence for the expression of such inactive Dnmt3b isoforms in the oocytes of the tested species.ConclusionsThe analysis of RNA-seq data and genomic sequences revealed that DNMT3L is likely to play a role in oocytes de novo DNA methylation only in mice, rats, gerbils and hamsters. The mechanism governing de novo DNA methylation in the oocytes of most mammalian species, including humans, occurs through a yet unknown mechanism that differs from the current model discovered in mouse.
| S-EPMC10625200 | biostudies-literature
Project description:Ultraconserved Elements Improve the Resolution of Difficult Nodes within the Rapid Radiation of Neotropical Sigmodontine Rodents (Cricetidae: Sigmodontinae).
| PRJEB43612 | ENA
Project description:Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin. DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain. Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a-Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a-Dnmt3L interface or the Dnmt3a-Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA-Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.
| S-EPMC2712830 | biostudies-literature
Project description:We used RRBS to analyze DNA methylation in mESC lines deficient for maternal Dnmt3L (Dnmt3L mKO), zygotic Dnmt3L (Dnmt3L KO), and both maternal and zygotic Dnmt3L (Dnmt3L mzKO). Compared to wild-type (WT) mESCs, Dnmt3L mKO mESCs exhibit severe loss of methylation at imprinted loci but no changes in global DNA methylation, Dnmt3L KO mESCs exhibit moderate loss of methylation at many Dnmt3a target regions but do not affect methylation at imprinted loci, and Dnmt3L mzKO mESCs exhibit combined changes of mKO and KO cells, with severe loss of methylation at imprinted loci and moderate loss of methylation at Dnmt3a target regions.
2018-10-04 | GSE116489 | GEO
Project description:Comparison of gene expression differences between Dnmt3L heterozygous and wildtype pachytene spermatocytes, and similarly between Dnmt3L heterozygous and wildtype round spermatids which were isolated from the Dnmt3L knockout mouse line. This array was conducted to address the hypothesis that Dnmt3L heterozygosity results in deregulated gene expression within spermatocytes and spermatids. Results show that Dnmt3L heterozygosity causes numerous genes to be differentially regulated on a genome-wide level, showing that DNMT3L has an important role in regulating gene expression within these male germ cells. Three preparations each of Dnmt3L purified wildtype spermatocytes, wildtype spermatids, heterozygous spermatids, and two preparations of heterozygous spermatocytes were isolated for a total of 11 samples. Each preparation was made up of cells isolated from 10 mice.
2011-03-01 | E-GEOD-20241 | biostudies-arrayexpress
Project description:Comparison of gene expression differences between Dnmt3L heterozygous and wildtype pachytene spermatocytes, and similarly between Dnmt3L heterozygous and wildtype round spermatids which were isolated from the Dnmt3L knockout mouse line. This array was conducted to address the hypothesis that Dnmt3L heterozygosity results in deregulated gene expression within spermatocytes and spermatids. Results show that Dnmt3L heterozygosity causes numerous genes to be differentially regulated on a genome-wide level, showing that DNMT3L has an important role in regulating gene expression within these male germ cells.
2011-03-01 | GSE20241 | 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. Keywords: genetic modification, DNA methylation
2008-04-14 | GSE8756 | GEO
Project description:We analyzed transcriptome profiles of postnatal germ cells and demonstrated that DNMT3L is important for spermatogonial stem/progenitor cell development Examination of wild-type and Dnmt3l knockout smaples in postnatal male germ cells
2014-07-03 | E-GEOD-54411 | biostudies-arrayexpress