Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA762589 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR15860076.fastq.gz | Fastqsanger.gz | |||
| SRR15860077.fastq.gz | Fastqsanger.gz | |||
| SRR15860078.fastq.gz | Fastqsanger.gz | |||
| SRR15860079.fastq.gz | Fastqsanger.gz |
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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
Project description:PRC2 mediates paternal epigenetic inheritance
| PRJNA282028 | ENA
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
Project description:Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present 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 using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-type F1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin.
| S-EPMC10359620 | biostudies-literature
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
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
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 | GSE68211 | GEO
Project description:Purpose: Paternal life experiences impact offspring health via germline, and epigenetic inheritance provides a potential mechanism. However, global reprogramming during offspring embryogenesis and gametogenesis represents the largest hurdle to conceptualize it. Yet, detailed characterization of how sperm epigenetic alterations carrying “environmental memory” can evade offspring embryonic reprogramming remains elusive. Methods: we profiled the sperm DNA methylation patterns of three consecutive generations (F0, F1 and F2) in both control and stress groups by using whole-genome bisulfite sequencing (WGBS). A total of 18 sperm samples were analyzed, including three biological replicates for each generation under each treatment. In addition, small RNA sequencing was carried out on paternal sperm samples to investigate whether long-term psychological stress affected the enrichment of certain sncRNAs and to identify whether they participated in mediating the occurrence and paternal inheritance of the stress-induced DMRs Rsults: Using an optimized data analysis workflow, we obtained approximately 800 million clean reads per sample (build mm10) with strand-specific coverage ~21×, and the data covered ~96.00% of the total 21,867,837 reference CpG dinucleotides. A total of 24,427, 7,975, and 5,173 differentially methylated regions (DMRs) between control and stress groups were found in the F0, F1, and F2 generations, respectively. Inter- and transgenerational inheritance of paternal DMRs were at frequencies approximately 11.36% and 0.48%, respectively. These DMRs related to genes with functional implications for psychological stress response, and tissue inheritance of these DMRs passed paternal disorders epigenetically to offspring. More importantly, these DMRs evaded offspring embryonic reprogramming through erasure and subsequent reestablishment, but not via un-erasure way. Nonetheless, their reestablishment proportions in the primitive streak (E7.5) stage were altered. Furthermore, sncRNA-seq revealed that stress-induced tsRNA, miRNA and rsRNA dysregulation in paternal sperm might play important roles in DMRs occurrence and paternal inheritance.
2021-10-11 | GSE185579 | GEO
Project description:PRC2 mediated paternal epigenetic inheritance - E15.5
| PRJEB24910 | ENA
Project description:RNA-seq transcriptome analysis of C. elegans germlines that inherited only paternal chromosomes (non-Mendelian inheritance, 'red-head worms') and the germlines of their offspring ('offspring of red-head worms') vs. germlines that inherited both maternal and paternal chromosomes (Mendelian inheritance, HBR1280 control). Given that epigenetic marking of sperm chromosomes is faithfully transmitted through embryo cell divisions, and that sperm epigenetic marking is important in offspring, we tested if sperm epigenetic marking alone is sufficient for proper development of the germline in offspring. We utilized a mutant that, during the first embryonic division, delivers the sperm genome to the daughter cell that generates the germline and the oocyte genome to the other daughter cell (Besseling & Bringmann, 2016). This mutant over-expresses GPR-1, a protein involved in regulation of kinetochore pulling forces. GPR-1 over-expression results in excessive pulling forces, causing the paternal and maternal pronuclei to inappropriately move to opposite poles of the 1-cell embryo instead of merging in the center of the embryo. In this mutant background, ~60% of offspring undergo atypical chromosome segregation, generating mosaic embryos whose germlines are derived entirely from sperm chromosomes (Besseling & Bringmann, 2016). To track the parental genomes, differentially tagged histone transgenes were used: a GFP-tagged histone H2B encoded in the sperm genome, and a TdTomato-tagged histone H2B encoded in the oocyte genome. The mosaic embryos whose germline inherited only sperm chromosomes (‘red-head' worms) develop into fertile adults with a normal brood size, similar to control worms, in which the germline inherited both sperm and oocyte chromosomes. RNA-seq analysis demonstrated that the germline transcriptome of ‘red-head’ worms and their offspring show few (<80 genes) and minor changes compared to control worms. These findings demonstrate that epigenetic information provided by sperm can guide proper germ cell development.
2018-07-23 | GSE115707 | GEO