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Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.

ABSTRACT: Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.

PROVIDER: PRJNA433940 | ENA |

REPOSITORIES: ENA

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Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.

Project description:Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood. Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance, both at the phenotypic and molecular levels. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in fetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control. Conclusion: This study reveals a novel role for the histone modifying complex, PRC2, in epigenetic inheritance, with important implications for understanding disease inheritance.

2018-02-15 | GSE110529 | GEO

PRC2 mediated paternal epigenetic inheritance

Project description:PRC2 mediated paternal epigenetic inheritance - E15.5

| PRJEB24910 | ENA

Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.

Project description: Not available

| S-EPMC6149058 | biostudies-literature

PRC2 8 cell embryo paternal epigenetic inheritance

Project description:PRC2 8 cell embryo paternal epigenetic inheritance

| PRJEB12268 | ENA

PRC2 mediated paternal epigenetic inheritance in day 8.5 embryos

Project description:PRC2 mediated paternal epigenetic inheritance in day 8.5 embryos

| PRJEB9120 | ENA

A membrane-associated condensate ensures paternal epigenetic inheritance in C. elegans

Project description:Transgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences. TEI allows priming of offspring towards changing environmental conditions and plays a role in the maintenance of gene silencing of selfish genetic elements like transposons. Small regulatory RNAs are well known to act in TEI, and can be transmitted via the male. Such inheritance via sperm requires dedicated mechanisms, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, which couples the paternal inheritance of a specific small RNA-bound silencing factor via S-palmitoylation to the transport of membranous organelles. Our findings uncover a thus far unknown paternal TEI mechanism, and describe a novel mode of transport of phase-separated condensates.

2021-03-26 | PXD019099 | Pride

PRC2 mediates paternal epigenetic inheritance: comparison of heterozygous mutant embryos

Project description:Determining the mechanisms that establish and regulate the transmission of non-genetic (i.e. epigenetic) information from parent to offspring is critical for understanding disease heredity. Using an innovative model to assess transmission of epigenetic effects, we provide evidence that Polycomb Repressive Complex 2 (PRC2) mediates inheritance through the male germline. This study reveals a novel role for histone modifying complexes in epigenetic inheritance, with important implications for understanding disease inheritance.

2018-02-09 | GSE68212 | GEO

PRC2 mediates paternal epigenetic inheritance: comparison of wild-type embryos

2018-02-09 | GSE68211 | GEO

Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin

Project description:Sperm chromatin retains small amounts of histones, and the chromatin states of sperm mirror gene expression programs of the next generation. It remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here we developed a novel mouse model of paternal epigenetic inheritance in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology, we rescued infertility of mice absent of Polycomb protein SCML2, which is the regulator of germline gene expression through the establishment of H3K27me3 on bivalent promoters with other active marks H3K4me2/3. In F1 males of Scml2-knockout mice, which has wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in mature sperm. Thus, SCML2 mediates intergenerational inheritance of paternal epigenetic information through the regulation of sperm chromatin.

2023-05-06 | GSE183994 | GEO

Genetic-epigenetic interactions in paternal transgenerational inheritance of metabolic disorders

Project description:Parental environmental exposures can strongly influence descendant risks for adult disease. Metabolic disorders arise from the intersection of environmental and genetic risk factors, with epigenetic inheritance being at the center of the familial cycle of transgenerational disease. How paternal high-fat diet changes the sperm chromatin leading to the acquisition of metabolic disease in offspring remains controversial and ill-defined. Using a genetic model of epigenetic inheritance, we investigated the role of histone H3 lysine 4 methylation (H3K4me3) in the paternal transmission of metabolic dysfunction. We show that obesity-induced alterations in sperm H3K4me3 associated with offspring phenotypes and corresponded to embryonic and placental chromatin profiles and gene expression. Transgenerational susceptibility to metabolic disease was only observed when grandsires had a pre-existing genetic predisposition to metabolic dysfunction that was associated with enhanced alterations to sperm H3K4me3. This non-DNA based knowledge of inheritance has the potential to improve our understanding of how environment shapes heritability and may lead to novel routes for the prevention of disease.

2022-03-30 | GSE178096 | GEO

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