Epigenetic programming of human sperm
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ABSTRACT:
PROVIDER: PRJNA656786 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic homogeneity underlies sperm programming for embryonic transcription single-ended ChIP-Seq libraries from sperm, egg extract (-geminin) treated sperm, egg extract (+geminin) treated sperm, and St 7 embryos with antibody for H3Kme3, H3K27me3, 3 replicates for each histone modification pull-down
2020-06-05 | GSE125982 | GEO
Project description:The WGBS data was published in PMID: 31393794 and the sequencing data from WGBS and MCC-Seq have been submitted to the European Genome-phenome Archive under the accession number EGAS00001003617. The paternal environment including stress, diet and toxicants has been linked to infertility and negative outcomes for offspring such as birth defects and adult onset of disease. Such effects may be transmitted via sperm through epigenetic mechanisms. To date, in depth profiling of the sperm epigenome in men has been limited. Our objective was to characterize the sperm profile of histone H3 lysine 4 tri-methylation (H3K4me3) from a reference population of men and relate this to sperm DNA methylation. ChIP-seq targeting H3K4me3 was performed on sperm from a representative reference population of 30 men and then overlapped with whole genome bisulfite sequencing (WGBS) data from the same men. Our analysis revealed that H3K4me3 is localized throughout the genome and at genes for fertility and development. Remarkably, enrichment was also found at regions that escape epigenetic reprogramming in primordial germ cells, embryonic enhancers and SINEs. The level of H3K4me3 in sperm associates with the degree of gene expression in embryo development. We find significant overlap in H3K4me3 and DNA methylation throughout the genome suggesting potential for the development of a personalized medicine approach for the assessment of fertility, lifestyle and environmental exposures.
2021-07-20 | GSE156108 | GEO
Project description:Epigenetic homogeneity underlies sperm programming for embryonic transcription
| PRJNA518148 | ENA
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. We show for the first time that remodelling of histones during spermiogenesis results in the retention of methylated histone H3 at the same genomic location in every sperm cell. This homogeneously methylated fraction of histone H3 in the sperm genome is maintained during early embryonic replication. Such methylated histone fraction resisting postfertilisation 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.
2020-05-29 | PXD012853 | Pride
Project description:Using the frog Xenopus laevis as a model system we profile epigenetic features of sperm and spermatid to study how they relate to gene expression in embryos. We observe that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks, at fertilization, deregulates gene expression in the resulting embryos in a paternal chromatin dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. 48 samples, single-ended ChIP-seq libraries from sperm- and spermatid-derived haploid embryos pulling down H3K4me2, H3K4me3, H3K27me3 and H3K9me3, 3 replicates for each histone modification pull-down. 14 samples of both single-ended and pair-ended RNA-seq libraries for sperm- and spermatid-derived embryos. 3 replicates of single-ended RNA-seq libraries for spermatid cells. 22 samples of single-ended RNA-seq form sperm- and spermatid-derived embryos overexpressing Kdm5b 16 samples of single-ended RNA-seq form sperm- and spermatid-derived embryos overexpressing Kdm6b 6 samples of single-ended MNase-seq from sperm and spermatid chromatin 12 samples of MBD-seq from sperm and spermatid chromatin
2016-03-22 | E-GEOD-75164 | biostudies-arrayexpress
Project description:The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure. Sperm were collected to examine differential DNA methylation regions (DMR) between the exposed and control populations. A statistically significant signature of DMRs was identified in the chemotherapy exposed male sperm. The DMRs, termed epimutations, were found in CpG desert regions of primarily 1 kilobase size. Gene associations and correlations to genetic mutations (copy number variation) were also investigated. Observations indicate adolescent chemotherapy exposure can promote epigenetic alterations that persist in later life. The germline (i.e. sperm) epimutations identified suggest chemotherapy has the potential to promote epigenetic inheritance to the next generation.
2016-10-01 | GSE85790 | GEO
Project description:Epigenetic programming of postnatal spermatogonia
| PRJNA521513 | ENA
Project description:Using the frog Xenopus laevis as a model system we profile epigenetic features of sperm and spermatid to study how they relate to gene expression in embryos. We observe that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks, at fertilization, deregulates gene expression in the resulting embryos in a paternal chromatin dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits.
2016-03-22 | GSE75164 | GEO
Project description:The environmental exposures and lifestyle of parents can alter the development of offspring. How this environmental information is coded into heritable messages to be transmitted by gametes remains unknown, but epigenetic mechanisms have been implicated. We recently determined that disruption of histone H3 di-methylation at lysine 4 (H3K4me2) in sperm has transgenerational consequences in the development of offspring. However, little is known about when in spermatogenesis histone methylation is established and whether epimutations induced in developing sperm are permanent. We hypothesize that epigenetic modifications to histones established in spermatogonia persist through spermatogenesis and can be transmitted to offspring via the sperm. Our objective was to determine what genomic regions bearing histone H3K4me2 in spermatogonia are also present in sperm. Methods: Using transgenic mice expressing Oct4-GFP, we isolated an enriched spermatogonia population and performed ChIP-seq for H3K4me2. Results: Our analysis revealed that H3K4me2 is located throughout the genome in spermatogonia and particularly at the transcription start site region (TSS) of more than 16,000 genes. Remarkably 44% of H3K4me2 peaks present in spermatogonia are conserved in sperm. The greatest overlap between spermatogonia and sperm occurred at the TSS with 83% similarity. Finally, we assessed the expression level of genes enriched in H3K4me2 in spermatogonia and sperm. We observed that genes with the highest enrichment in H3K4me2 in sperm are expressed at higher levels in spermatogenesis and during development. Conclusion: These findings suggest that if epimutations are induced in spermatogonia they may persist in sperm and influence the health and development of offspring.
2019-04-30 | GSE126303 | GEO
Project description:BACKGROUND: In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function. METHODS AND RESULTS: Sperm DNA and mRNA were isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNA methylation was measured with the Illumina Infinium array at 27,000 CpG loci. Unsupervised clustering of methylation data differentiated the 21 sperm samples by their motility values. Recursively partitioned mixture modeling (RPMM) of methylation data resulted in four distinct methylation profiles that were significantly associated with sperm motility (P=0.01). Linear models of microarray analysis (LIMMA) was performed based on motility and identified 9,189 CpG loci with significantly altered methylation (Q<0.05) in the low motility samples, with many loci located in genes associated with subfertility and epigenetic regulation. In the low motility samples, the majority of disrupted CpG loci (80%) were hypomethylated. Of the aberrantly methylated CpGs, 194 were associated with imprinted genes almost equally distributed into hypermethylated (predominantly paternally expressed) and hypomethylated (predominantly maternally expressed) groups. Sperm mRNA was measured with the Human Gene 1.0 ST Affymetrix GeneChip Array. LIMMA analysis based on motility identified 20 candidate transcripts as differentially expressed in low motility sperm, including HDAC1 (NCBI 3065), SIRT3 (NCBI 23410), and DNMT3A (NCBI 1788). Altered expression of these epigenetic regulatory genes was associated with RPMM DNA methylation class. CONCLUSIONS: Using integrative genome-wide approaches to study epigenetic and gene expression patterns in human sperm we identified CpG methylation profiles and mRNA alterations associated with low sperm motility, and that low motility sperm may have aberrant genome-wide hypomethylation due to excess HDAC1 activity. See "summary" above
2011-06-02 | E-GEOD-26881 | biostudies-arrayexpress