Mammalian sperm exhibit epigenetic priming of embryonic and adult regulatory landscapes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79230 | GEO | 2017/01/17
SECONDARY ACCESSION(S): PRJNA315212
REPOSITORIES: GEO
Similar Datasets
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79226 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79229 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79225 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79227 | GEO
Project description:Mammalian sperm exhibit epigenetic priming of embryonic and adult regulatory landscapes
| PRJNA315212 | ENA
Project description:The mammalian sperm genome is thought to lack substantial information for the regulation of future expression after fertilization. Here, we show that most promoters in mouse sperm are flanked by well-positioned nucleosomes marked by active histone modifications. Analysis of these modifications suggests that many enhancers and super-enhancers functional in embryonic and adult tissues are already specified in sperm. The sperm genome is bound by CTCF and cohesin at sites that are also present in round spermatids and embryonic stem cells (ESCs). These sites mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results suggest that sperm carry a rich source of regulatory information, encoded in part by its three-dimensional folding specified by CTCF and cohesin. This information may contribute to future expression during embryonic and adult life, suggesting mechanisms by which environmental effects on the paternal germline are transmitted transgenerationally.
| S-EPMC5313040 | biostudies-literature
Project description:Sperm contributes genetic and epigenetic information to the embryo to efficiently support development. However, the mechanism underlying such developmental competence remains elusive. Here, we investigated whether all sperm cells have a common epigenetic configuration that primes transcriptional program for embryonic development. Using calibrated ChIP-seq, we show that remodelling of histones during spermiogenesis results in the retention of methylated histone H3 at the same genomic location in most sperm cell. This homogeneously methylated fraction of histone H3 in the sperm genome is maintained during early embryonic replication. Such methylated histone fraction resisting post-fertilisation reprogramming marks developmental genes whose expression is perturbed upon experimental reduction of histone methylation. A similar homogeneously methylated histone H3 fraction is detected in human sperm. Altogether, we uncover a conserved mechanism of paternal epigenetic information transmission to the embryo through the homogeneous retention of methylated histone in a sperm cells population.
| S-EPMC7359334 | biostudies-literature
Project description:Hepatocellular carcinomas (HCCs) usually arise from chronic liver disease (CLD). Precancerous cells in chronically inflamed environments may be 'epigenetically primed', sensitising them to oncogenic transformation. We investigated whether epigenetic priming in CLD may affect HCC outcomes by influencing the genomic and transcriptomic landscapes of HCC. Analysis of DNA methylation arrays from 10 paired CLD-HCC identified 339 shared dysregulated CpG sites and 18 shared differentially methylated regions compared with healthy livers. These regions were associated with dysregulated expression of genes with relevance in HCC, including ubiquitin D (UBD), cytochrome P450 family 2 subfamily C member 19 (CYP2C19) and O-6-methylguanine-DNA methyltransferase (MGMT). Methylation changes were recapitulated in an independent cohort of nine paired CLD-HCC. High CLD methylation score, defined using the 124 dysregulated CpGs in CLD and HCC in both cohorts, was associated with poor survival, increased somatic genetic alterations and TP53 mutations in two independent HCC cohorts. Oncogenic transcriptional and methylation dysregulation is evident in CLD and compounded in HCC. Epigenetic priming in CLD sculpts the transcriptional landscape of HCC and creates an environment favouring the acquisition of genetic alterations, suggesting that the extent of epigenetic priming in CLD could influence disease outcome.
| S-EPMC8807355 | biostudies-literature
Project description:Embryonic pluripotency in the mouse is established and maintained by a gene-regulatory network under the control of a core set of transcription factors that include octamer-binding protein 4 (Oct4; official name POU domain, class 5, transcription factor 1, Pou5f1), sex-determining region Y (SRY)-box containing gene 2 (Sox2), and homeobox protein Nanog. Although this network is largely conserved in eutherian mammals, very little information is available regarding its evolutionary conservation in other vertebrates. We have compared the embryonic pluripotency networks in mouse and chick by means of expression analysis in the pregastrulation chicken embryo, genomic comparisons, and functional assays of pluripotency-related regulatory elements in ES cells and blastocysts. We find that multiple components of the network are either novel to mammals or have acquired novel expression domains in early developmental stages of the mouse. We also find that the downstream action of the mouse core pluripotency factors is mediated largely by genomic sequence elements nonconserved with chick. In the case of Sox2 and Fgf4, we find that elements driving expression in embryonic pluripotent cells have evolved by a small number of nucleotide changes that create novel binding sites for core factors. Our results show that the network in charge of embryonic pluripotency is an evolutionary novelty of mammals that is related to the comparatively extended period during which mammalian embryonic cells need to be maintained in an undetermined state before engaging in early differentiation events.
| S-EPMC2993340 | biostudies-literature
Project description:BackgroundReactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive to ROS damaging effects because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. However, how oxidative DNA lesions in sperm affect early embryonic development remains elusive.ResultsUsing cattle as model, we show that fertilization using sperm exposed to oxidative stress caused a major developmental arrest at the time of embryonic genome activation. The levels of DNA damage response did not directly correlate with the degree of developmental defects. The early cellular response for DNA damage, γH2AX, is already present at high levels in zygotes that progress normally in development and did not significantly increase at the paternal genome containing oxidative DNA lesions. Moreover, XRCC1, a factor implicated in the last step of base excision repair (BER) pathway, was recruited to the damaged paternal genome, indicating that the maternal BER machinery can repair these DNA lesions induced in sperm. Remarkably, the paternal genome with oxidative DNA lesions showed an impairment of zygotic active DNA demethylation, a process that previous studies linked to BER. Quantitative immunofluorescence analysis and ultrasensitive LC-MS-based measurements revealed that oxidative DNA lesions in sperm impair active DNA demethylation at paternal pronuclei, without affecting 5-hydroxymethylcytosine (5hmC), a 5-methylcytosine modification that has been implicated in paternal active DNA demethylation in mouse zygotes. Thus, other 5hmC-independent processes are implicated in active DNA demethylation in bovine embryos. The recruitment of XRCC1 to damaged paternal pronuclei indicates that oxidative DNA lesions drive BER to repair DNA at the expense of DNA demethylation. Finally, this study highlighted striking differences in DNA methylation dynamics between bovine and mouse zygotes that will facilitate the understanding of the dynamics of DNA methylation in early development.ConclusionsThe data demonstrate that oxidative stress in sperm has an impact not only on DNA integrity but also on the dynamics of epigenetic reprogramming, which may harm the paternal genetic and epigenetic contribution to the developing embryo and affect embryo development and embryo quality.
| S-EPMC6192351 | biostudies-literature