scholarly journals Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sangeetha Mahadevan ◽  
Varsha Sathappan ◽  
Budi Utama ◽  
Isabel Lorenzo ◽  
Khalied Kaskar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Subcellular Localization ◽  
Crucial Role ◽  
Preimplantation Embryos ◽  
Maternal Genome ◽  
Embryonic Loss ◽  
Cytoplasmic Complex ◽  
Zygotic Genome

Abstract Mammalian parental genomes contribute differently to early embryonic development. Before activation of the zygotic genome, the maternal genome provides all transcripts and proteins required for the transition from a highly specialized oocyte to a pluripotent embryo. Depletion of these maternally-encoded transcripts frequently results in failure of preimplantation embryonic development, but their functions in this process are incompletely understood. We found that female mice lacking NLRP2 are subfertile because of early embryonic loss and the production of fewer offspring that have a wide array of developmental phenotypes and abnormal DNA methylation at imprinted loci. By demonstrating that NLRP2 is a member of the subcortical maternal complex (SCMC), an essential cytoplasmic complex in oocytes and preimplantation embryos with poorly understood function, we identified imprinted postzygotic DNA methylation maintenance, likely by directing subcellular localization of proteins involved in this process, such as DNMT1, as a new crucial role of the SCMC for mammalian reproduction.

scholarly journals Maternal SMCHD1 controls both imprinted Xist expression and imprinted X chromosome inactivation

2021 ◽  
Author(s):  
Iromi Wanigasuriya ◽  
Sarah A Kinkel ◽  
Tamara Beck ◽  
Ellise A Roper ◽  
Kelsey Breslin ◽  
...  
Keyword(s):  
Embryonic Development ◽  
X Chromosome ◽  
Preimplantation Embryo ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Preimplantation Embryos ◽  
Xist Expression ◽  
Critical Window ◽  
Zygotic Genome

Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1's role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling.

scholarly journals Expression and Potential Role of microRNA-29b in Mouse Early Embryo Development

2015 ◽  
Vol 35 (3) ◽  
pp. 1178-1187 ◽  
Author(s):  
Junqiang Zhang ◽  
Ying Wang ◽  
Xiaoguang Liu ◽  
Shenglin Jiang ◽  
Chun Zhao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Dna Methyltransferase ◽  
Biological Function ◽  
Expression Patterns ◽  
Early Embryo ◽  
Early Embryonic Development ◽  
Preimplantation Embryos ◽  
Early Embryos

Background/Aims: MicroRNA-29b (miR29b) has been previously identified in early mouse embryos through miRNA microarray analysis. Recent research has indicated that miR29b participates in DNA methylation by regulating DNA methyltransferase 3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological function of miR29b in mouse preimplantation embryonic development remain unknown. Methods: In this study, we examined the expression patterns of miR29b and Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently, expression and localization of DNMT3A/3B protein was analyzed in mouse early embryos by immunofluorescence staining. The biological function of miR29b in mouse early embryos was analyzed by microinjection of commercially available miRNA-specific inhibitors and mimics. Results: Our data showed that Dnmt3a/3b mRNA expression is negatively regulated by miR29b in mouse early embryos. Immunofluorescence analysis revealed that DNMT3A/3B protein expression is predominantly localized within the nucleoplasm of embryos. Alterations to the activity of miR29b could change the DNA methylation levels in mouse preimplantation embryos and lead to a developmental blockade, from the morula to the blastocyst stage. Conclusion: These results indicated a role for the miR29b-Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we provide evidence that miR29b is indispensable for mouse early embryonic development. This study contributes to a preliminary understanding of the role of miR29b during mouse embryonic development.

scholarly journals Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes

2021 ◽  
Author(s):  
Qian-Qian Sha ◽  
Ye-Zhang Zhu ◽  
Yunlong Xiang ◽  
Jia-Li Yu ◽  
Xiao-Ying Fan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone H3 ◽  
Finger Protein ◽  
Maternal Genome ◽  
Wide Range ◽  
Transcriptional Changes ◽  
Nuclear Events ◽  
Genomic Regions ◽  
Cxxc Finger Protein 1

Abstract During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.

scholarly journals Discovery of pluripotency-associated microRNAs in rabbit preimplantation embryos and embryonic stem-like cells

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 421-437 ◽  
Author(s):  
Pouneh Maraghechi ◽  
László Hiripi ◽  
Gábor Tóth ◽  
Babett Bontovics ◽  
Zsuzsanna Bősze ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Blastocyst Stage ◽  
Expression Level ◽  
Preimplantation Embryos ◽  
Regulatory Function ◽  
Low Level ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple biological processes. Increasing experimental evidence implies an important regulatory role of miRNAs during embryonic development and in embryonic stem (ES) cell biology. In the current study, we have described and analyzed the expression profile of pluripotency-associated miRNAs in rabbit embryos and ES-like cells. The rabbit specific ocu-miR-302 and ocu-miR-290 clusters, and three homologs of the human C19MC cluster (ocu-miR-512, ocu-miR-520e, and ocu-miR-498) were identified in rabbit preimplantation embryos and ES-like cells. The ocu-miR-302 cluster was highly similar to its human homolog, while ocu-miR-290 revealed a low level of evolutionary conservation with its mouse homologous cluster. The expression of the ocu-miR-302 cluster began at the 3.5 days post-coitum early blastocyst stage and they stayed highly expressed in rabbit ES-like cells. In contrast, a high expression level of the ocu-miR-290 cluster was detected during preimplantation embryonic development, but a low level of expression was found in rabbit ES-like cells. Differential expression of the ocu-miR-302 cluster and ocu-miR-512 miRNA was detected in rabbit trophoblast and embryoblast. We also found that Lefty has two potential target sites in its 3′UTR for ocu-miR-302a and its expression level increased upon ocu-miR-302a inhibition. We suggest that the expression of the ocu-miR-302 cluster is characteristic of the rabbit ES-like cell, while the ocu-miR-290 cluster may play a crucial role during early embryonic development. This study presents the first identification, to our knowledge, of pluripotency-associated miRNAs in rabbit preimplantation embryos and ES-like cells, which can open up new avenues to investigate the regulatory function of ocu-miRNAs in embryonic development and stem cell biology.

Role of peptidylarginine deiminase 4 (PAD4) in pig parthenogenetic preimplantation embryonic development

Zygote ◽  
2012 ◽  
Vol 21 (4) ◽  
pp. 385-393
Author(s):  
Manjula Brahmajosyula ◽  
Masashi Miyake
Keyword(s):  
Gene Regulation ◽  
Embryonic Development ◽  
Normal Development ◽  
Preimplantation Embryos ◽  
Peptidylarginine Deiminase ◽  
Stages Of Development ◽  
Developmental Arrest ◽  
Slow Development ◽  
Arginine Modification

SummaryArginine modification to citrulline (citrullination) is catalyzed by peptidylarginine deiminases (PADs) and one of the isomers PAD4 is shown to be involved in the gene regulation. In our previous paper we studied the localization and expression of PAD4 and the target of PAD4 in mammalian gametes and preimplantation embryos. In this study the role of PAD4 was examined in the pig diploid parthenogenetic preimplantation embryonic development. Knockdown of PAD4 by RNAi resulted in delayed development. Inhibition of PAD4 by a potent PAD4 inhibitor Cl-amidine from the time of activation for 24 h resulted in developmental arrest at the first cleavage. Inhibition at the later stages of development resulted in delayed or arrested development. A shorter exposure to Cl-amidine for 6 h at any stage of growth resulted in slow development. Thus, this study suggests that PAD4 activity is essential for the normal development of the embryos.

scholarly journals Crucial Role of DNA Methylation in Determination of Clonally Distributed Killer Cell Ig-like Receptor Expression Patterns in NK Cells

2002 ◽  
Vol 169 (8) ◽  
pp. 4253-4261 ◽  
Author(s):  
Simeon Santourlidis ◽  
Hans-Ingo Trompeter ◽  
Sandra Weinhold ◽  
Britta Eisermann ◽  
Klaus L. Meyer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nk Cells ◽  
Crucial Role ◽  
Expression Patterns ◽  
Killer Cell ◽  
Receptor Expression

scholarly journals Knockdown of Dnmt1 links Gene body DNA methylation to regulation of gene expression and maternal-zygotic transition in the wasp Nasonia

2021 ◽  
Author(s):  
Deanna Arsala ◽  
Xin Wu ◽  
Soojin V. Yi ◽  
Jeremy A. Lynch
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Regulation Of Gene Expression ◽  
Gene Body ◽  
Nasonia Vitripennis ◽  
Gene Body Methylation ◽  
Genome Bisulfite Sequencing ◽  
Genome Activation ◽  
Zygotic Genome

AbstractGene body methylation (GBM) is an ancestral form of DNA methylation whose role in development has remained unclear. Unlike vertebrates, DNA methylation is found exclusively in gene bodies in the wasp Nasonia vitripennis, which provides a unique opportunity to interpret the role of GBM in development. We confirmed that parental RNAi (pRNAi) knockdown of a DNMT1 ortholog (Nv-Dnmt1a) in Nasonia leads to embryonic lethality and failures in cellularization and morphogenesis. Using whole-genome bisulfite sequencing, we found a widespread loss of GBM in Nv-Dnmt1a pRNAi embryos. Using RNAseq, we found that methylated genes that lost GBM in the pRNAi samples were exclusively downregulated during zygotic genome activation. Unexpectedly, nearly all affected unmethylated genes were up-regulated after pRNAi. Lack of proper clearance of mRNAs and abnormal activation drive this up-regulation, indicating critical roles for Nv-Dnmt1a and GBM in the maternal-zygotic transition (MZT) in the wasp, despite their absence in Drosophila.

scholarly journals The DNA-to-cytoplasm ratio broadly activates zygotic gene expression in Xenopus

2021 ◽  
Author(s):  
David Jukam ◽  
Rishabh Kapoor ◽  
Aaron F Straight ◽  
Jan Skotheim
Keyword(s):  
Cycle Duration ◽  
Zygotic Genome Activation ◽  
Maternal Genome ◽  
Tropicalis Genome ◽  
Nuclear Component ◽  
Zygotic Gene ◽  
Component C ◽  
Genome Activation ◽  
Zygotic Genome

In multicellular animals, the first major event after fertilization is the switch from maternal to zygotic control of development. During this transition, zygotic gene transcription is broadly activated in an otherwise quiescent genome in a process known as zygotic genome activation (ZGA). In fast developing embryos, ZGA often overlaps with the slowing of initially synchronous cell divisions at the mid-blastula transition (MBT). Initial studies of the MBT led to the nuclear-to-cytoplasmic ratio model where MBT timing is regulated by the exponentially increasing amounts of some nuclear component N titrated against a fixed cytoplasmic component C. However, more recent experiments have been interpreted to suggest that ZGA is independent of the N/C ratio. To determine the role of the N/C ratio in ZGA, we generated Xenopus frog embryos with ~3-fold differences in genomic DNA (i.e., N) by using X. tropicalis sperm to fertilize X. laevis eggs with or without their maternal genome. Resulting embryos have otherwise identical X. tropicalis genome template amounts, embryo sizes, and X. laevis maternal environments. We used the X. tropicalis paternally derived mRNA to identify a high confidence set of exclusively zygotic transcripts. Both ZGA and the increase in cell cycle duration are delayed in embryos with ~3-fold less DNA per cell. Thus, DNA is an important component of the N/C ratio, which is indeed a critical regulator of zygotic genome activation in Xenopus embryos.

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