Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation
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ABSTRACT:
PROVIDER: PRJNA562501 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10024571_1.fastq.gz | Fastqsanger.gz | |||
| SRR10024571_2.fastq.gz | Fastqsanger.gz | |||
| SRR10024572_1.fastq.gz | Fastqsanger.gz | |||
| SRR10024572_2.fastq.gz | Fastqsanger.gz | |||
| SRR10024573_1.fastq.gz | Fastqsanger.gz |
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Project description:We performed ATAC-seq in mouse sperms and fertilized eggs with wild-type or P1 mutation (phosphorylation sites by SRPK1) to capture early genome reprogramming events ~5 hours post insemination. Surprisingly, we detected broadly distributed ATAC-seq reads across the mouse genome to paternal and maternal gametes formed with wild-type and single mutant sperm, and in contrast, we saw individual peaks with zygotes formed with the double mutant sperm. After assigning to paternal and maternal genomes, we found that the reads assignable to paternal genome was decreased with single and double mutants, compare with wild-type. Furthermore, we found the paternal genome in eggs fertilized with the double mutant sperm essentially retained all sperm-specific ATAC-seq peaks, which were also overlapped with the published H3.3 ChIP-seq signals on wild-type sperm, mostly corresponding to TSSs. Strikingly, the ATAC-seq signals on the maternal genome from eggs fertilized with the double mutant P1 sperm were literally identical to those in MII oocyte. Based on these data, we draw two important conclusions: (i) dramatic chromatin remodeling takes place in a highly coordinated fashion in both paternal and maternal pronuclei before they merge, and (ii) SRPK1-catalyzed protamine phosphorylation initiates such synchronized genome reprogramming in both gametes.
2020-03-16 | GSE136403 | GEO
Project description:The paternal genome undergoes a massive exchange of histone with protamine for compaction into sperm during spermiogenesis. Upon fertilization, this process is potently reversed, which is essential for parental genome reprogramming and subsequent activation; however, it remains poorly understood how this fundamental process is initiated and regulated. Here, we report that the previously characterized splicing kinase SRPK1 initiates this life-beginning event by catalyzing site-specific phosphorylation of protamine, thereby triggering protamine-to-histone exchange in the fertilized oocyte. Interestingly, protamine undergoes a DNA-dependent phase transition to gel-like condensates and SRPK1-mediated phosphorylation likely helps open up such structures to enhance protamine dismissal by nucleoplasmin (NPM2) and enable the recruitment of HIRA for H3.3 deposition. Remarkably, genome-wide assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis reveals that selective chromatin accessibility in both sperm and MII oocytes is largely erased in early pronuclei in a protamine phosphorylation-dependent manner, suggesting that SRPK1-catalyzed phosphorylation initiates a highly synchronized reorganization program in both parental genomes.
| S-EPMC7190278 | biostudies-literature
Project description:The glycolytic enzyme, pyruvate kinase Pyk1 maintains telomere heterochromatin by phosphorylating histone H3T11 (H3pT11), which promotes SIR (silent information regulator) complex binding at telomeres and prevents autophagy-mediated Sir2 degradation. However, the exact action mechanism of H3pT11 is poorly understood. Here, we identify Dot1-catalyzed H3K79 tri-methylation (H3K79me3) as the downstream effector of H3pT11 and uncover how this histone crosstalk regulates autophagy and telomere silencing. Mechanistically, Pyk1-catalyzed H3pT11 directly reduces the binding of Dot1 to chromatin and inhibits Dot1-catalyzed H3K79me3, which leads to transcriptional repression of autophagy genes and reduced autophagy. Despite the antagonism between H3pT11 and H3K79me3, they synergically promote the binding of SIR complex at telomeres to maintain telomere silencing. Furthermore, we identify Reb1 as a telomere-associated factor that recruits Pyk1-containing SESAME (Serine-responsive SAM-containing Metabolic Enzyme) complex to telomere regions to phosphorylate H3T11 and prevent the invasion of H3K79me3 from euchromatin into heterochromatin to maintain telomere silencing. Together, these results uncover a novel histone crosstalk and provide insights into dynamic regulation of silent heterochromatin and autophagy in response to cell metabolism.
2022-11-29 | GSE210908 | GEO
Project description:SESAME-catalyzed H3T11 phosphorylation inhibits Dot1-catalyzed H3K79me3 to regulate autophagy and telomere silencing
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Project description:By using RNA-Seq technology, we get genome-wide transcriptome profiles of cloned and in vivo fertilized porcine embryos, from the oocyte to the blastocyst stages. We identified differentially expressed genes between the cloned and in vivo fertilized embryos from distinct stages of development and uncovered associated cellular signaling pathways and upstream transcription factors.
2019-04-29 | GSE125706 | GEO
Project description:Unique chromatin remodeling factors orchestrate dramatic changes in nuclear morphology during differentiation of the mature sperm head. A critical step in this process is histone-to-protamine exchange, which must be executed correctly to avoid sperm DNA damage, embryonic lethality, and male sterility. Here, we define an essential role for the histone methyltransferase DOT1L in the histone-to-protamine transition. We show that DOT1L is abundantly expressed in meiotic and postmeiotic germ cells and that methylation of histone H3 lysine 79 (H3K79), the modification catalyzed by DOT1L, is enriched in developing spermatids in the initial stages of histone replacement. Elongating spermatids lacking DOT1L fail to fully replace histones and exhibit aberrant protamine recruitment, resulting in deformed sperm heads and male sterility. Loss of DOT1L results in transcriptional dysregulation coinciding with the onset of histone replacement and affecting genes required for histone-to-protamine exchange. DOT1L also deposits H3K79me2 and promotes accumulation of elongating RNA Polymerase II at the testis-specific bromodomain gene Brdt. Together, our results indicate that DOT1L is an important mediator of transcription during spermatid differentiation and an indispensable regulator of male fertility.
2023-03-22 | GSE217931 | GEO
Project description:Eggs contain about 200,000 mitochondria that generate ATP and metabolites essential for oocyte and embryo development. In addition to this energetic role, mitochondria also integrate the cellular metabolic and transcriptional state via metabolites which regulate epigenetic modifiers. The maternal epigenome is established during oogenesis, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and embryo development. The DRP1 protein is required for mitochondrial fission. Here, we demonstrate a dramatic maternal effect in that DRP1-deficient oocytes fertilized by wild-type sperm exhibit a high frequency of failure in peri- and post-implantation development. This failure is associated with altered oocyte mitochondrial function, changes in the oocyte transcriptome and proteome, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting the pronuclei of these fertilized oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.
2021-11-01 | GSE180579 | GEO
Project description:The study of genomic imprinting in mammals started with analysis of parthenogenetic embryos. At the phenotypic level, embryos with two maternal genomes and no paternal genome proceed through early development unimpaired, and only begin to fail after implantation. The most recognizable early defect is reduced or non-existent trophoblast, the tissue that gives rise to the placenta. We applied the procedure for establishing Trophoblast Stem cells (TS cells) developed in the Rossant lab to parthenogenetic embryos, and were successful in making four different TS cell lines, three from MI oocyte derived blastocysts and one from MII derived blastocysts. Initial molecular characterization, including microarray analysis, indicates that these cells are indistinguishable from fertilized TS cells, with the single exception of null expression of the paternally expressed gene Snrpn. The only significant difference between parthenogenetic and fertilized TS cells was the frequency with which they could be derived. In our hands, fertilized blastocyst outgrowths produced TS cells at robust rates (10-12 colonies per blastocyst), while parthenogenetic blastocyst outgrowths produced only 4 colonies in 50 outgrowths, 100 times less frequently than fertilized embryos. This led us to hypothesize that those few TS cells that arose in parthenogenetic outgrowths were probably a result of very low frequency stochastic variation in the imprint status of a gene or genes required for either establishment or maintenance of stem cells, or both. The corollary to this hypothesis posits that the early failure of parthenogenetic embryos, and in particular parthenogenetic trophoblast, is a function of impaired stem cell function. This raises the intriguing possibility that microarray comparisons of parthenogenetic, fertilized and androgenetic blastocysts may reveal the identities of genes important for stem cell biology. To this end, my colleague Keith Latham, at the Fels Institute, Temple University, Philadelphia, made amplified cDNAs from pools of ten each of androgenetic, gynogenetic, or fertilized blastocysts. Three separate pools for each type of embryo were prepared for microarray analysis. The embryos were all produced by nuclear transfers between zygotes, a difficult technique that is Keith's special expertise. He used the Brady/Iscove protocol to generate quantitative 3' end biased cDNAs. We would like to compare the transcriptomes of these embryos using the MOE430 2.0 arrays. We expect that important insights into the biology of uniparental embryos in general, and stem cells in particular may be revealed. Keywords: other
2007-12-01 | GSE8163 | GEO
Project description:Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by passive electrostatics between DNA and the arginine-rich core of protamines. However, phylogenetic analysis reveals several non-arginine residues that are conserved within, but not across, species. The functional significance of these residues or post-translational modifications are poorly understood. In this experiment, we investigated the presence of post-translational modifications on mouse protamine 1 to begin to dissect their function in vivo.
2023-05-17 | PXD028917 | Pride
Project description:The study of genomic imprinting in mammals started with analysis of parthenogenetic embryos. At the phenotypic level, embryos with two maternal genomes and no paternal genome proceed through early development unimpaired, and only begin to fail after implantation. The most recognizable early defect is reduced or non-existent trophoblast, the tissue that gives rise to the placenta. We applied the procedure for establishing Trophoblast Stem cells (TS cells) developed in the Rossant lab to parthenogenetic embryos, and were successful in making four different TS cell lines, three from MI oocyte derived blastocysts and one from MII derived blastocysts. Initial molecular characterization, including microarray analysis, indicates that these cells are indistinguishable from fertilized TS cells, with the single exception of null expression of the paternally expressed gene Snrpn. The only significant difference between parthenogenetic and fertilized TS cells was the frequency with which they could be derived. In our hands, fertilized blastocyst outgrowths produced TS cells at robust rates (10-12 colonies per blastocyst), while parthenogenetic blastocyst outgrowths produced only 4 colonies in 50 outgrowths, 100 times less frequently than fertilized embryos. This led us to hypothesize that those few TS cells that arose in parthenogenetic outgrowths were probably a result of very low frequency stochastic variation in the imprint status of a gene or genes required for either establishment or maintenance of stem cells, or both. The corollary to this hypothesis posits that the early failure of parthenogenetic embryos, and in particular parthenogenetic trophoblast, is a function of impaired stem cell function. This raises the intriguing possibility that microarray comparisons of parthenogenetic, fertilized and androgenetic blastocysts may reveal the identities of genes important for stem cell biology. To this end, my colleague Keith Latham, at the Fels Institute, Temple University, Philadelphia, made amplified cDNAs from pools of ten each of androgenetic, gynogenetic, or fertilized blastocysts. Three separate pools for each type of embryo were prepared for microarray analysis. The embryos were all produced by nuclear transfers between zygotes, a difficult technique that is Keith's special expertise. He used the Brady/Iscove protocol to generate quantitative 3' end biased cDNAs. We would like to compare the transcriptomes of these embryos using the MOE430 2.0 arrays. We expect that important insights into the biology of uniparental embryos in general, and stem cells in particular may be revealed. Experiment Overall Design: this experiment include 3 samples and 18 replicates
2008-06-16 | E-GEOD-8163 | biostudies-arrayexpress