scholarly journals De Novo DNA Methylation in the Male Germ Line Occurs by Default but Is Excluded at Sites of H3K4 Methylation

Cell Reports ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 205-219 ◽  
Author(s):  
Purnima Singh ◽  
Arthur X. Li ◽  
Diana A. Tran ◽  
Nathan Oates ◽  
Eun-Rim Kang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Germ Line ◽  
H3k4 Methylation ◽  
Male Germ Line

Mammalian DNMTs in the male germ line DNA of Drosophila

2008 ◽  
Vol 86 (5) ◽  
pp. 380-385 ◽  
Author(s):  
Alexandra Weyrich ◽  
Xiaojing Tang ◽  
Guoliang Xu ◽  
André Schrattenholz ◽  
Christian Hunzinger ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Drosophila Melanogaster ◽  
Functional Role ◽  
De Novo ◽  
Germ Line ◽  
Dna Methyltransferases ◽  
Male Germ Line ◽  
Nuclear Regions ◽  
Functional Relevance

It is controversial whether DNA methylation plays a functional role in Drosophila . We have studied testis DNA of Drosophila melanogaster Meigen, 1830 with antisera against 5-methylcytosine (5mC) and found no evidence for the presence of significant amounts of 5mC. Reactions occur only with 1 of 3 5mC antisera, but they are restricted to nuclear regions without detectable amounts of DNA. The antisera apparently cross-react with other nuclear components. If the murine de novo DNA methyltransferases, DNMT3A and DNMT3B, are expressed under the control of the spermatocyte-specific β2-tubulin promoter in testes, DNA methylation is not increased and no effects on the fertility of the fly are seen. DNA methylation has, therefore, no functional relevance in the male germ line of Drosophila.

scholarly journals Epigenetic marking and repression of porcine endogenous retroviruses

2013 ◽  
Vol 94 (5) ◽  
pp. 960-970 ◽  
Author(s):  
Gernot Wolf ◽  
Anders Lade Nielsen ◽  
Jacob Giehm Mikkelsen ◽  
Finn Skou Pedersen
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Germ Line ◽  
Mammalian Species ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Primer Binding Site ◽  
Retroviral Transduction ◽  
Embryonic Germ Cells ◽  
Epigenetic Repression

Endogenous retroviruses (ERVs) are remnants of retroviral germ line infections and have been identified in all mammals investigated so far. Although the majority of ERVs are degenerated, some mammalian species, such as mice and pigs, carry replication-competent ERVs capable of forming infectious viral particles. In mice, ERVs are silenced by DNA methylation and histone modifications and some exogenous retroviruses were shown to be transcriptionally repressed after integration by a primer-binding site (PBS) targeting mechanism. However, epigenetic repression of porcine ERVs (PERVs) has remained largely unexplored so far. In this study, we screened the pig genome for PERVs using LTRharvest, a tool for de novo detection of ERVs, and investigated various aspects of epigenetic repression of three unrelated PERV families. We found that these PERV families are differentially up- or downregulated upon chemical inhibition of DNA methylation and histone deacetylation in cultured porcine cells. Furthermore, chromatin immunoprecipitation analysis revealed repressive histone methylation marks at PERV loci in primary porcine embryonic germ cells and immortalized embryonic kidney cells. PERV elements belonging to the PERV-γ1 family, which is the only known PERV family that has remained active up to the present, were marked by significantly higher levels of histone methylations than PERV-γ2 and PERV-β3 proviruses. Finally, we tested three PERV-associated PBS sequences for repression activity in murine and porcine cells using retroviral transduction experiments and showed that none of these PBS sequences induced immediate transcriptional silencing in the tested primary porcine cells.

Changes in DNA methylation during mouse embryonic development in relation to X-chromosome activity and imprinting

1990 ◽  
Vol 326 (1235) ◽  
pp. 299-312 ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
X Chromosome ◽  
De Novo ◽  
Germ Line ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromatin Configuration ◽  
Methylation Patterns

Changing DNA methylation patterns during embryonic development are discussed in relation to differential gene expression, changes in X-chromosome activity and genomic imprinting. Sperm DNA is more methylated than oocyte DNA, both overall and for specific sequences. The methylation difference between the gametes could be one of the mechanisms (along with chromatin structure) regulating initial differences in expression of parental alleles in early development. There is a loss of methylation during development from the morula to the blastocyst and a marked decrease in methylase activity. De novo methylation becomes apparent around the time of implantation and occurs to a lesser extent in extra-embryonic tissue DNA. In embryonic DNA, de novo methylation begins at the time of random X-chromosome inactivation but it continues to occur after X-chromosome inactivation and may be a mechanism that irreversibly fixes specific patterns of gene expression and X-chromosome inactivity in the female. The germ line is probably delineated before extensive de novo methylation and hence escapes this process. The marked undermethylation of the germ line DNA may be a prerequisite for X-chromosome reactivation. The process underlying reactivation and removal of parent-specific patterns of gene expression may be changes in chromatin configuration associated with meiosis and a general reprogramming of the germ line to developmental totipotency.

scholarly journals Promoter-Dependent Mechanism Leading to Selective Hypomethylation within the 5′ Region of Gene MAGE-A1 in Tumor Cells

2004 ◽  
Vol 24 (11) ◽  
pp. 4781-4790 ◽  
Author(s):  
Charles De Smet ◽  
Axelle Loriot ◽  
Thierry Boon
Keyword(s):  
Tumor Cells ◽  
De Novo ◽  
Germ Line ◽  
Male Germ Line ◽  
Site Specific ◽  
Local Inhibition ◽  
Genome Wide ◽  
Somatic Tissues ◽  
Dependent Mechanism

ABSTRACT Several male germ line-specific genes, including MAGE-A1, rely on DNA methylation for their repression in normal somatic tissues. These genes become activated in many types of tumors in the course of the genome-wide demethylation process which often accompanies tumorigenesis. We show that in tumor cells expressing MAGE-A1, the 5′ region is significantly less methylated than the other parts of the gene. The process leading to this site-specific hypomethylation does not appear to be permanent in these tumor cells, since in vitro-methylated MAGE-A1 sequences do not undergo demethylation after being stably transfected. However, in these cells there is a process that inhibits de novo methylation within the 5′ region of MAGE-A1, since unmethylated MAGE-A1 transgenes undergo remethylation at all CpGs except those located within the 5′ region. This local inhibition of methylation appears to depend on promoter activity. We conclude that the site-specific hypomethylation of MAGE-A1 in tumor cells relies on a transient process of demethylation followed by a persistent local inhibition of remethylation due to the presence of transcription factors.

scholarly journals Detailed profiles of histone modification in male germ line cells of the young and aged mice

2019 ◽  
Author(s):  
Misako Tatehana ◽  
Ryuichi Kimura ◽  
Kentaro Mochizuki ◽  
Noriko Osumi
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Histone Modifications ◽  
Sex Chromosomes ◽  
De Novo ◽  
Germ Line ◽  
Epidemiological Studies ◽  
De Novo Mutations ◽  
Male Germ Line ◽  
M Phase

Human epidemiological studies have shown paternal aging as one of the risks for neurodevelopmental disorders such as autism in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence biology of offspring. Here we are focusing on epigenetic alterations in sperm that can influence offspring developmental programs. In this study, we qualitatively and semi-quantitatively evaluated histone modification patterns in male germ line cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months) and aged (12 months) old mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, H3K9me3 was decreased in the male germ line cells in the aged testis, while H3K27me2/3 was increased. The intensity of H3K27ac, an active mark, was relatively low in the aged testis. Interestingly, H3K27ac was detected in putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germ line cells in the aged testis. H3K79me3 was contrastingly increased and accumulated on the sex chromosomes at M-phase spermatocytes. Therefore, aging induced alterations in the amount of histone modifications, of which patterns were different in individual histone modifications. Moreover, histone modification seems to be differentially regulated by aging on the sex chromosomes and on others. These findings would help elucidate epigenetic mechanisms underlying influence of paternal aging on offspring's development.

scholarly journals In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Marco Morselli ◽  
William A Pastor ◽  
Barbara Montanini ◽  
Kevin Nee ◽  
Roberto Ferrari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Gene Body ◽  
Mammalian Development ◽  
H3k4 Methylation ◽  
H3k36 Methylation ◽  
Male Germline ◽  
Yeast Strains ◽  
Dna Methylation Analysis

Methylation of cytosines (5meC) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5meC levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.

scholarly journals Timing and Sequence Requirements Defined for Embryonic Maintenance of Imprinted DNA Methylation at Rasgrf1

2006 ◽  
Vol 26 (24) ◽  
pp. 9564-9570 ◽  
Author(s):  
Rebecca Holmes ◽  
Yanjie Chang ◽  
Paul D. Soloway
Keyword(s):  
Dna Methylation ◽  
Germ Line ◽  
Direct Repeat ◽  
Repeat Sequence ◽  
Paternal Allele ◽  
Imprinted Genes ◽  
Male Germ Line ◽  
Specific Expression ◽  
Morula Stage ◽  
Allele Specific

ABSTRACT Epigenetic programming is critical for normal development of mammalian embryos. Errors cause misexpression of genes and aberrant development (E. Li, C. Beard, and R. Jaenisch, Nature 366:362-365, 1993). Imprinted genes are important targets of epigenetic regulation, but little is known about how the epigenetic patterns are established in the parental germ lines and maintained in the embryo. Paternal allele-specific expression at the imprinted Rasgrf1 locus in mice is controlled by paternal allele-specific methylation at a differentially methylated domain (DMD). DMD methylation is in turn controlled by a direct repeat sequence immediately downstream of the DMD which is required for establishing Rasgrf1 methylation in the male germ line (B. J. Yoon et al., Nat. Genet. 30:92-96, 2002). To determine if these repeats have a role in methylation maintenance, we developed a conditional deletion of the repeat sequence in mice and showed that the repeats are also required during a narrow interval to maintain paternal methylation of Rasgrf1 in developing embryos. Removing the repeats upon fertilization caused a total loss of methylation by the morula stage, but by the epiblast stage, the repeats were completely dispensable for methylation maintenance. This developmental interval coincides with genome-wide demethylation and remethylation in mice which most imprinted genes resist. Our data show that the Rasgrf1 repeats serve at least two functions: first, to establish Rasgrf1 DNA methylation in the male germ line, and second, to resist global demethylation in the preimplantation embryo.

scholarly journals Dynamic Methylation of an L1 Transduction Family during Reprogramming and Neurodifferentiation

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Carmen Salvador-Palomeque ◽  
Francisco J. Sanchez-Luque ◽  
Patrick R. J. Fortuna ◽  
Adam D. Ewing ◽  
Ernst J. Wolvetang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
De Novo ◽  
Germ Line ◽  
Somatic Mosaicism ◽  
Induced Pluripotent Stem Cell ◽  
Early Embryo ◽  
Individual Genome ◽  
Induced Pluripotent

ABSTRACT The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neuronal lineage and cause somatic mosaicism. Although DNA methylation mediates L1 promoter repression, the temporal pattern of methylation applied to individual RC-L1s during neurogenesis is unclear. Here, we identified a de novo L1 insertion in a human induced pluripotent stem cell (hiPSC) line via retrotransposon capture sequencing (RC-seq). The L1 insertion was full-length and carried 5ʹ and 3ʹ transductions. The corresponding donor RC-L1 was part of a large and recently active L1 transduction family and was highly mobile in a cultured-cell L1 retrotransposition reporter assay. Notably, we observed distinct and dynamic DNA methylation profiles for the de novo L1 and members of its extended transduction family during neuronal differentiation. These experiments reveal how a de novo L1 insertion in a pluripotent stem cell is rapidly recognized and repressed, albeit incompletely, by the host genome during neurodifferentiation, while retaining potential for further retrotransposition.

scholarly journals Estrogen signaling, through estrogen receptor β, regulates DNA methylation and its machinery in male germ line in adult rats

Epigenetics ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. 476-483 ◽  
Author(s):  
Kushaan Dumasia ◽  
Anita Kumar ◽  
Sharvari Deshpande ◽  
Nafisa H. Balasinor
Keyword(s):  
Dna Methylation ◽  
Estrogen Receptor ◽  
Germ Line ◽  
Estrogen Receptor Β ◽  
Estrogen Signaling ◽  
Male Germ Line ◽  
Adult Rats

302 IMPRINTED microRNA ARE DIFFERENTIALLY EXPRESSED IN ADULT MOUSE TESTES-DERIVED MALE GERM-LINE STEM CELLS

2011 ◽  
Vol 23 (1) ◽  
pp. 248
Author(s):  
J. Y. Shin ◽  
Y. H. Jung ◽  
M. K. Gupta ◽  
S. J. Uhm ◽  
S. T. Shin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Germ Line ◽  
Es Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Male Germ Line ◽  
Comparison Results ◽  
Differentiation Stage

Testis-derived male germ-line stem (GS) cells, the in vitro counterpart of spermatogonial stem cells, can acquire multipotency under appropriate culture conditions to become multipotent adult germ-line stem (maGS) cells, which, upon testicular transplantation, produce teratomas instead of initiating spermatogenesis. This study evaluated the DNA methylation and expression of imprinted microRNA (miRNA) in mouse GS and maGS cells. The GS and maGS cell lines were established essentially as described earlier (Jung et al. 2010 Mol. Hum. Reprod. PMID: 20610616) and were quantified for maternally (miR-296-3p, miR-296-5p, miR-483) and paternally (miR-127, miR-127-5p) imprinted miRNA by real-time TaqMan® MicroRNA assay and for DNA methylation at imprinting control regions of respective miRNA (Gnas-Nespas DMR, Igf2-H19 ICR, and Dlk1-Dio3 IG-DMR) by bisulfite genomic sequencing. Sperm and embryonic stem (ES) cells were used as controls for comparison. Results showed that, similar to sperm, expression of maternally imprinted miRNA was consistently higher (P < 0.001), whereas that of paternally imprinted miRNA was consistently lower (P < 0.001) in GS cells than in control ES cells. The DNA methylation analyses further confirmed that imprinted miRNA were androgenetic in GS cells. On the other hand, DNA methylation of maGS cells resembled that of ES cells, but the expression pattern of imprinted miRNA was intermediate between that of GS cells and ES cells. The expression of imprinted miRNA in GS and maGS cells was also altered during their in vitro differentiation but varied with both the differentiation stage and the miRNA. In conclusion, our data suggest that GS cells have androgenetic DNA methylation and expression of imprinted miRNA which changes to an ES cell-like pattern upon their conversion to maGS cells and, therefore, may serve as an epigenetic miRNA signature or molecular marker to distinguish GS cells from maGS cells. This work was supported by a grant (Code #200901FHT010305191) from BioGreen 21 Program, RDA, Republic of Korea.

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