The effect of the Pld6 and Dnmt3l mutations on DNA methylation and expression of retrotransposons in mouse male germ cells
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ABSTRACT:
PROVIDER: PRJNA289866 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2102030.fastq.gz | Fastqsanger.gz | |||
| SRR2102040_1.fastq.gz | Fastqsanger.gz | |||
| SRR2102040_2.fastq.gz | Fastqsanger.gz | |||
| SRR2102050.fastq.gz | Fastqsanger.gz | |||
| SRR2102031.fastq.gz | Fastqsanger.gz |
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Project description:Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs called piRNAs combat retrotransposon activity. The piRNA system guides de novo DNA methylation at retrotransposon promoters, but it remains unclear whether DNA methylation is involved in retrotransposon silencing in prospermatogonia. We performed a genome-wide study of DNA methylation and RNA abundance for retrotransposons in developing mouse male germ cells, using Pld6/Mitopld and Dnmt3l knockout (KO) mice deficient in piRNA biogenesis and de novo DNA methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation at most retrotransposons but its effect on their RNA abundance was low in prospermatogonia. In the Pld6 mutants, only few retrotransposons exhibited reduced DNA methylation but many were more upregulated at the RNA level than in the Dnmt3l mutants. Moreover, the retrotransposon upregulation by the Pld6 mutation was observed even in the Dnmt3l KO background. Thus, in prospermatogonia, post-transcriptional RNA digestion by the piRNA system plays a more important role in retrotransposon regulation than transcriptional silencing by DNA methylation. However, their relative importance was changed in meiotic spermatocytes where hypomethylation of retrotransposons increased their expression by up to 100-fold in both mutants. Interestingly, retrotransposon activation disrupted the transcriptome integrity because intergenic and intronic retrotransposon sequences, in particular, the antisense promoter of LINE-1, drive expression of nearby genes.
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Project description:Patterns of DNA methylation are established during gametogenesis. The catalytically-inactive adaptor Dnmt3L is crucial to ensure this occurs correctly. In vitro, Dnmt3L binds to the N terminal tail of histone H3 but the function of this interaction during development is unknown. Here we show that Dnmt3L-histone H3 interaction is necessary for spermatogenesis. Mutant animals exhibit reduced fertility, defective methylation establishment at retrotransposons coupled with their reactivation and meiotic catastrophe. The spermatogonial stem cell pool is also defective, with mutant cells displaying marked changes in gene expression. Genome-wide methylation analysis reveals reductions in CG methylation as well as severe loss of non-CG methylation suggesting that non-CG methylation is specifically sensitive to the ability of Dnmt3L to bind histone H3. MethylC-Seq of wild-type and Dnmt3LA/A 1dpp prospermatagonia
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Project description:DNA methyltransferase 3A (DNMT3A) and DNA methyltransferase 3-Like (DNMT3L) form functional heterotetramers and ATRX-DNMT3-DNMT3L (ADD) domains, shared by both DNMT3A and DNMT3L, recognizes histone H3 tail unmethylated at lysine-4 (H3K4me0) to deposit DNA methylation properly in mammalian germ cells. However, the combinational and differential role of ADD domains of DNMT3A and DNMT3L in vivo has not been fully defined. Here we analyze both female and male germ cells derived from mouse with amino-acid substitutions in ADD domains of DNMT3A and/or DNMT3L that impair their domain function. Loss of either DNMT3A-ADD or DNMT3L-ADD domain function shows moderate reduction of global CG methylation level, but in different degree, in both germ cells. However, when both DNMT3A and DNMT3L lost their ADD domain functions, reduction of the global CG methylation level is much more severe and comparable with that of Dnmt3a/3L knockout germ cells. In contrast, such double mutant germ cells have thousands of genomic regions where non-CG methylation is aberrantly accumulated. These results highlight a critical role of the combinational function of ADD domains for the robust CG and non-CG methylation in germ cells.
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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
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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.
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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.
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Project description:We analyzed transcriptome profiles of postnatal germ cells and demonstrated that DNMT3L is important for spermatogonial stem/progenitor cell development
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