Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1097619 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28589385_1.fastq.gz | Fastqsanger.gz | |||
| SRR28589385_2.fastq.gz | Fastqsanger.gz | |||
| SRR28589386_1.fastq.gz | Fastqsanger.gz | |||
| SRR28589386_2.fastq.gz | Fastqsanger.gz | |||
| SRR28589387_1.fastq.gz | Fastqsanger.gz |
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Project description:The male mammalian germline is characterized by two rounds of significant chromatin remodeling of the genome, first by the histone-to-protamine transition during spermatogenesis, followed by the reversal to nucleo-histones in the male pronucleus of the zygote. Both transitions are associated with the extensive formation of DNA double-strand breaks (DSBs), requiring an estimated 5 to 10 million transient DSBs per spermatozoa. Additionally, the high transcription rate in early stages of spermatogenesis leads to transcription-coupled damage preceding meiotic homologous recombination, potentially further contributing to the DSB landscape in mature spermatozoa. Once meiosis is completed, spermatozoa remain haploid and therefore cannot rely on error-free homologous recombination, but instead depend on error-prone classical non-homologous end joining (cNHEJ). This DNA damage/repair-scenario is proposed to be one of the main causes of the observed paternal mutation propensity in human evolution. Recent studies have shown that DSBs in the male pronucleus are repaired by maternally provided Polθ in C. elegans through Polθ-mediated end joining (TMEJ). Additionally, population genetic datasets have revealed a preponderance of TMEJ signatures associated with human variation. Since these signatures are the result of the combined effect of TMEJ and DSB formation in spermatozoa and male pronuclei, we used a BLISS-based protocol to analyze recurrent DSBs in mature human sperm heads as a proxy of the male pronucleus before zygotic chromatin remodeling. The DSBs were found to be enriched in (YR)n short tandem repeats and in evolutionarily young SINEs, reminiscent to patterns observed in murine spermatids, indicating evolutionary hotspots of recurrent DSB formation in mammalian spermatozoa. Additionally, we detected a similar DSB pattern in diploid human IMR90 cells when cNHEJ was selectively inhibited, indicating the significant impact of absent cNHEJ on the sperm DSB landscape. Strikingly, regions associated with most retained histones, and therefore less condensed chromatin, were not strongly enriched with recurrent DSBs. In contrast, the fraction of retained H3K27me3 in the mature spermatozoa displayed a strong association with recurrent DSBs. DSBs in H3K27me3 are associated with a preference for TMEJ over cNHEJ during repair. We hypothesize that the retained H3K27me3 may trigger transgenerational DNA repair by priming maternal Polθ to these regions.
2024-06-19 | GSE269135 | GEO
Project description:A study utilizing next-generation sequencing provided a comprehensive expression profile of murine spermatozoa, revealing the transcriptional landscape of mature sperm isolated from the corpus and cauda epididymides of C57BL/6 mice. By analyzing RNA content, we identified a distinct set of retained transcripts, including those encoding sperm-specific ion channels, as well as transcripts associated with sperm motility, capacitation, and the acrosome reaction. In addition to spermatozoa, the study also reported the transcriptional profiling of murine leukocytes, providing comparative insights into cell-type-specific gene expression. This study advances our understanding of sperm transcriptomics and its implications for male fertility
2025-04-02 | GSE290696 | GEO
Project description:Small noncoding RNAs (sncRNA) are becoming recognized for their participation in a diverse range of cellular functions. In this study, their global characterization in human spermatozoa from donors with proven fertility was undertaken. Reads were analyzed in two classes, those mapping to unique locations and those that could be aligned to up to 10 genomic locations. All libraries showed comparable distribution of reads between intergenic, intronic and exonic genomic regions. Analysis of the sequences revealed the presence of multiple small RNA classes. The miRNAs retained in spermatozoa were found to be associated with promoter regions, suggestive of a role at the transcriptional level. Piwi-interacting sncRNAs as well as repeat-associated small RNAs were identified for the first time in mature spermatozoa from a mammalian species. Human spermatozoa retain a multifaceted population of small non-coding RNAs. Their presence is consistent with the view that they may function to stabilize the genome as part of the confrontation and consolidation of the genomes at fertilization.
2011-10-16 | GSE21191 | GEO
Project description:Small noncoding RNAs (sncRNA) are becoming recognized for their participation in a diverse range of cellular functions. In this study, their global characterization in human spermatozoa from donors with proven fertility was undertaken. Reads were analyzed in two classes, those mapping to unique locations and those that could be aligned to up to 10 genomic locations. All libraries showed comparable distribution of reads between intergenic, intronic and exonic genomic regions. Analysis of the sequences revealed the presence of multiple small RNA classes. The miRNAs retained in spermatozoa were found to be associated with promoter regions, suggestive of a role at the transcriptional level. Piwi-interacting sncRNAs as well as repeat-associated small RNAs were identified for the first time in mature spermatozoa from a mammalian species. Human spermatozoa retain a multifaceted population of small non-coding RNAs. Their presence is consistent with the view that they may function to stabilize the genome as part of the confrontation and consolidation of the genomes at fertilization. Examination of sperm samples from 3 individuals, sequenced individually
2011-10-15 | E-GEOD-21191 | biostudies-arrayexpress
Project description:Chromatin undergoes major remodeling around DNA double strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high resolution map of gammaH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit from the cohesin complex, previously characterized as required for repair by homologous recombination. We found that the recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs. In addition, we show that the cohesin complex, which was also recently proposed to be a key player in chromosome organisation and chromatin looping, controls gammaH2AX distribution within domains. Indeed, as we reported for transcription, cohesin binding antagonizes gammaH2AX spreading. Remarkably, depletion of cohesin leads to an increase of gammaH2AX at cohesin-bound genes (revelead by gammaH2AX mapping in upon SCC1 siRNA), associated with a decrease in their expression level after DSB induction. Thus our study identifies a novel role for the cohesin complex in protecting the genes located in gammaH2AX domains from both gammaH2AX spreading and transcriptional shut-down after DSB induction.
2012-01-01 | E-TABM-1164 | biostudies-arrayexpress
Project description:Calcium influx is a critical event in mammalian fertilization, but the molecular mechanisms that govern the calcium dynamics in spermatozoa in response to physiological stimuli are still poorly understood. In the present work we analyze the role of the Ca2+-dependent transcriptional repressor DREAM (downstream regulatory element antagonist modulator) in spermatozoa using a transgenic mouse line that express a dominant constitutively active DREAM mutant. Genome-wide expression analysis of transgenic mice showed that DREAM modulates gene expression throughout the maturation process of sperm from spermatogonia to mature spermatozoa.
2020-02-01 | GSE27829 | GEO
Project description:Spermatozoa deliver a complex and environment sensitive pool of small non-coding RNAs (sncRNA) to the oocyte at fertilisation, which influences offspring development and adult phenotypic trajectories. Whether mature spermatozoa in the epididymis can directly sense the environment is still not fully understood. Here, we used two distinct paradigms of preconception acute High Fat Diet challenge to dissect epididymal vs spermatogenic contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNA fragments as sperm-born sensors. In human spermatozoa, we found mt-tsRNAs in linear association with BMI and showed that paternal overweight at conception is sufficient to double offspring obesity risk and compromise metabolic health. Using mouse genetics and metabolic phenotypic data, we show that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction in mice. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tsRNAs at fertilisation and implied them in the control of early embryo metabolism. Our study supports the importance of paternal health at conception for offspring metabolism, propose mt-tsRNAs as sperm-born environmental effectors of paternal inheritance and demonstrate, for the first time in a physiological and unperturbed setting, father-to-offspring transfer of sperm mt-tsRNAs at fertilisation.
2024-04-03 | GSE239810 | GEO
Project description:Genome-wide DNA methylation profile of human spermatozoa using the meDIP technique and massively parallel sequencing
2008-05-31 | E-TABM-482 | biostudies-arrayexpress
Project description:Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double strand break (DSB) formation, but the role and precise landscape of histone modifications at hotspots remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is strikingly elevated, and H3K4me3 is not significantly enriched. Remarkably, elimination of H3K9ac reduced binding of the DSB-inducing enzyme Rec12 and DSB at hotspots. We also found that the H3K4 metyltransferase Set1 promotes DSB formation at some loci, but it restricts Rec12 binding to hotspots. These results suggest that H3K9ac rather than H3K4me3 is a hotspot-associated mark involved in meiotic DSB formation in fission yeast.
2013-03-07 | GSE31648 | GEO