Large, Male Germ Cell-Specific Hypomethylated DNA Domains With Unique Genomic and Epigenomic Features on the Mouse X Chromosome

Ikeda, Rieko; Shiura, Hirosuke; Numata, Koji; Sugimoto, Michihiko; Kondo, Masayo; Mise, Nathan; Suzuki, Masako; Greally, John M.; Abe, Kuniya

doi:10.1093/dnares/dst030

Cited by 10 publications

(11 citation statements)

References 43 publications

(90 reference statements)

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“…Our data are in support of differential regulation prior to meiosis. Consistent with our findings, a recent study demonstrated that duplicated regions that are enriched on the X chromosome are hypomethylated and enriched with H3K9me2 in the germline prior to meiosis [ 32 ]. It could be intriguing to further investigate the details about inherent differences between the X chromosome and autosomes in the germline.…”

Section: Discussionsupporting

confidence: 92%

Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline

et al. 2015

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BackgroundThe male germline transcriptome changes dramatically during the mitosis-to-meiosis transition to activate late spermatogenesis genes and to transiently suppress genes commonly expressed in somatic lineages and spermatogenesis progenitor cells, termed somatic/progenitor genes.ResultsThese changes reflect epigenetic regulation. Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization. Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3.ConclusionsOur results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0159-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline

et al. 2015

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“…The existence of PMDs is consistent with the previous observation that whole testis DNA tends to have more hypomethylated CG sites in low GC content regions than in somatic tissues [ 40 ]. In addition, some PMDs that we found in X chromosome were identical to the previously reported large hypomethylated domains or LoDs [ 41 ] (Additional file 2 : Figure S3).…”

Section: Resultssupporting

confidence: 87%

DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis

et al. 2015

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BackgroundIn the male germline, neonatal prospermatogonia give rise to spermatogonia, which include stem cell population (undifferentiated spermatogonia) that supports continuous spermatogenesis in adults. Although the levels of DNA methyltransferases change dynamically in the neonatal and early postnatal male germ cells, detailed genome-wide DNA methylation profiles of these cells during the stem cell formation and differentiation have not been reported.ResultsTo understand the regulation of spermatogonial stem cell formation and differentiation, we examined the DNA methylation and gene expression dynamics of male mouse germ cells at the critical stages: neonatal prospermatogonia, and early postntal (day 7) undifferentiated and differentiating spermatogonia. We found large partially methylated domains similar to those found in cancer cells and placenta in all these germ cells, and high levels of non-CG methylation and 5-hydroxymethylcytosines in neonatal prospermatogonia. Although the global CG methylation levels were stable in early postnatal male germ cells, and despite the reported scarcity of differential methylation in the adult spermatogonial stem cells, we identified many regions showing stage-specific differential methylation in and around genes important for stem cell function and spermatogenesis. These regions contained binding sites for specific transcription factors including the SOX family members.ConclusionsOur findings show a distinctive and dynamic regulation of DNA methylation during spermatogonial stem cell formation and differentiation in the neonatal and early postnatal testes. Furthermore, we revealed a unique accumulation and distribution of non-CG methylation and 5hmC marks in neonatal prospermatogonia. These findings contrast with the reported scarcity of differential methylation in adult spermatogonial stem cell differentiation and represent a unique phase of male germ cell development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1833-5) contains supplementary material, which is available to authorized users.

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“…Microarray analysis of purified mouse PGCs was performed as described44. Expression levels of ovo -like genes and other germline markers were extracted from the microarray data.…”

Section: Methodsmentioning

confidence: 99%

Conserved role of Ovo in germline development in mouse and Drosophila

Hayashi

Shinozuka

Shigenobu

et al. 2017

Sci Rep

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Ovo, which encodes a transcription factor with Zn-finger domains, is evolutionarily conserved among animals. In Drosophila, in addition to its zygotic function for egg production, maternal ovo activity is required in primordial germ cells (PGCs) for expression of germline genes such as vasa and nanos. In this study, we found that maternal Ovo accumulates in PGC nuclei during embryogenesis. In these cells, ovo serves a dual function: activation of genes expressed predominantly in PGCs, and conversely suppression of somatic genes. Reduction of ovo activity in PGCs makes them unable to develop normally into germ cells of both sexes. In mice, knockout of the ovo ortholog, Ovol2, which is expressed in PGCs, decreases the number of PGCs during early embryogenesis. These data strongly suggest that ovo acts as part of an evolutionarily conserved mechanism that regulates germline development in animals.

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Large, Male Germ Cell-Specific Hypomethylated DNA Domains With Unique Genomic and Epigenomic Features on the Mouse X Chromosome

Cited by 10 publications

References 43 publications

Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline

Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline

DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis

Conserved role of Ovo in germline development in mouse and Drosophila

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