Essential Role of Mg2+ for Mouse Preimplantation Embryo Development Revealed by TRPM7 Chanzyme Deficient Gametes
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ABSTRACT:
PROVIDER: PRJNA1008261 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25732500_1.fastq.gz | Fastqsanger.gz | |||
| SRR25732500_2.fastq.gz | Fastqsanger.gz | |||
| SRR25732501_1.fastq.gz | Fastqsanger.gz | |||
| SRR25732501_2.fastq.gz | Fastqsanger.gz | |||
| SRR25732502_1.fastq.gz | Fastqsanger.gz |
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Project description:TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx is indispensable for reaching the blastocyst stage. TRPM7 was expressed dynamically from gametes to blastocysts, displaying stage-specific and distinct localizations on the plasma membrane, cytoplasm, and nucleus, and undergoes cleavage that produces C- terminal kinase fragments. TRPM7 underpinned Mg2+ homeostasis throughout this time, and excess Mg2+ but not Zn2+ or Ca2+ overcame the arrest of Trpm7-null embryos; expressing Trpm7 mRNA restored development, but mutant versions failed or were less effective. Transcriptomic analyses of embryos lacking Trpm7 revealed an abundance of oxidative stress-pathway genes, confirmed by mitochondrial dysfunction, and a reduction of transcription factor networks essential for proliferation; Mg2+ supplementation corrected these defects. Hence, TRPM7 underpins Mg2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell lineage specification.
2024-01-22 | GSE241487 | GEO
Project description:TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx is indispensable for reaching the blastocyst stage. TRPM7 is expressed dynamically from gametes to blastocysts; displays stage-specific localization on the plasma membrane, cytoplasm, and nucleus; and undergoes cleavage that produces C-terminal kinase fragments. TRPM7 underpins Mg2+ homeostasis, and excess Mg2+ but not Zn2+ or Ca2+ overcomes the arrest of Trpm7-null embryos; expressing Trpm7 mRNA restores development, but mutant versions fail or are partially rescued. Transcriptomic analyses of Trpm7-null embryos reveal an abundance of oxidative stress-pathway genes, confirmed by mitochondrial dysfunction, and a reduction in transcription factor networks essential for proliferation; Mg2+ supplementation corrects these defects. Hence, TRPM7 underpins Mg2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell-lineage specification.
| S-EPMC10842026 | biostudies-literature
Project description:Magnesium is essential for cellular life, but how it is homeostatically controlled still remains poorly understood. Here we report that members of CNNM family, which have been controversially implicated in both cellular Mg2+ influx and efflux, selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. Co-expression of CNNMs with the channel markedly increased uptake of divalent cations, which is prevented by an inactivating mutation to the channel’s pore. Knockout of Trpm7 in cells or application of the TRPM7-channel inhibitor NS8593 also interfered with CNNM-stimulated divalent cation uptake. Conversely, knockout of CNNM3 and CNNM4 in HEK-293 cells significantly reduced TRPM7-mediated divalent cation entry, without affecting TRPM7 protein expression or its cell surface levels. Furthermore, we found that cellular overexpression of Phosphatases of Regenerating Liver (PRLs), a known CNNMs binding partner, stimulated TRPM7-dependent divalent cation entry and that CNNMs were required for this activity. Whole-cell electrophysiological recordings demonstrated that deletion of CNNM3 and CNNM4 from HEK-293 cells interfered with heterologously expressed and native TRPM7 channel function. We conclude that CNNMs employ the TRPM7 channel to mediate divalent cation influx and that CNNMs also possess separate TRPM7-independent Mg2+ efflux activities that contribute to CNNMs’ control of cellular Mg2+ homeostasis.
2021-11-15 | PXD026635 | Pride
Project description:The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of an ion channel domain and an intracellularly located protein kinase domain. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative MS analysis. We found that native TRPM7 channels are high molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels.
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Project description:DNA methylomes of the bovine gametes and in vivo preimplantation embryos
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Project description:DNA methylation is an important epigenetic modification that undergoes dynamic changes in mammalian embryogenesis, during which both parental genomes are reprogrammed. Despite the many immunostaining studies that have assessed global methylation, the gene-specific DNA methylation patterns in bovine preimplantation embryos are unknown. Using reduced representation bisulfite sequencing, we determined genome-scale DNA methylation patterns of bovine sperm and individual in vivo developed oocytes and preimplantation embryos. We show that: 1) the major wave of genome-wide demethylation was completed by the 8-cell stage; 2) promoter methylation was significantly and inversely correlated with gene expression at the 8-cell and blastocyst stages; 3) sperm and oocytes have numerous differentially methylated regions (DMRs) - DMRs specific for sperm were strongly enriched in long terminal repeats (LTRs) and rapidly lost methylation in embryos, while the oocyte-specific DMRs were more frequently localized in exons and CpG islands (CGIs) and demethylated gradually across cleavage stages; 4) a unique set of DMRs were found between in vivo and in vitro matured oocytes; and 5) differential methylation between bovine gametes was confirmed in some but not all known imprinted genes. Our data provide insights into deciphering the complex epigenetic reprogramming of bovine early embryos and will serve as an important model for investigating human development and the evolutionary and regulatory roles of DNA methylation.
2018-08-01 | GSE110400 | GEO
Project description:Analysis of the effect of shRNA-mediated knockdown of TRPM7 on gene expression levels in SH-SY5Y and SH-EP2 human neuroblastoma cells. Results were used for the identification of neural-crest-associated transcription factors that were affected by TRPM7 knockdown. Total RNA isolated from SH-EP2 and SH-SY5Y human neuroblastoma cells transduced with a scrambled shRNA (control) or TRPM7 shRNA, experiment performed in duplicate.
2014-12-10 | E-GEOD-64000 | biostudies-arrayexpress
Project description:The functional activity of TRPM7 is essential for cell viability and growth, and its expression is up-regulated in certain pathological conditions. In order to assess the effects of TRPM7 activity on cellular gene expression, inducible HEK293 cell-lines harboring the wild-type mouse TRPM7 and a mutant lacking the kinase domain were established. By using microarray analysis, we identified genetic profiles altered in transcription significantly and specifically by the expression of the functional TRPM7 channel. Overexpression of TRPM7 channel in HEK cells induce the cell damage and cell death. So we used tetracycline-inducible system for channel expression. However, since the treatment of inducer itself could also affect the transcription profile, we established another cell-line harboring a nonfunctional TRPM7 mutant (TRPM7DKD) as a control in which the entire kinase domain at the C-terminus was deleted. The wild-type and the non-functional TRPM7 channels were induced transiently, and the comparative changes in cellular transcription were investigated
2011-07-22 | E-GEOD-23102 | biostudies-arrayexpress
Project description:Mechanisms by which the mammalian gametes encode epigenetic information that can be transmitted to the progeny are relatively unknown. We find that many sperm promoters in mouse sperm are occupied by phosphorylated forms of RNA polymerase II and the Mediator complex. Analysis of ATAC-seq data suggest that the same promoters are occupied by components of the transcription complex in GV and MII oocytes and preimplantation embryos. Furthermore, distal ATAC-seq sites containing transcription factor motifs are conserved in monkeys and humans. ChIP-seq analyses confirm that transcription factors, including FoxA1 and the androgen and estrogen receptors, occupy distal enhancers. These sites and their interactions with promoters in the gametes are maintained in the early embryo. Additionally, sperm- or oocyte-specific interactions mediated by CTCF/cohesin are only present in the paternal or maternal chromosome, respectively in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. These results suggest that the mammalian gametes contain a large repertoire of transcription factors that organize a complex pattern of 3D interactions and can be transmitted to the zygote after fertilization.
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Project description:Mechanisms by which the mammalian gametes encode epigenetic information that can be transmitted to the progeny are relatively unknown. We find that many sperm promoters in mouse sperm are occupied by phosphorylated forms of RNA polymerase II and the Mediator complex. Analysis of ATAC-seq data suggest that the same promoters are occupied by components of the transcription complex in GV and MII oocytes and preimplantation embryos. Furthermore, distal ATAC-seq sites containing transcription factor motifs are conserved in monkeys and humans. ChIP-seq analyses confirm that transcription factors, including FoxA1 and the androgen and estrogen receptors, occupy distal enhancers. These sites and their interactions with promoters in the gametes are maintained in the early embryo. Additionally, sperm- or oocyte-specific interactions mediated by CTCF/cohesin are only present in the paternal or maternal chromosome, respectively in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. These results suggest that the mammalian gametes contain a large repertoire of transcription factors that organize a complex pattern of 3D interactions and can be transmitted to the zygote after fertilization.
2019-02-28 | GSE116855 | GEO