Genome plasticity in the mouse oocyte and early embryo

2007 ◽  
Vol 35 (3) ◽  
pp. 618-622 ◽  
Author(s):  
A.E. Peaston ◽  
B.B. Knowles ◽  
K.W. Hutchison
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Early Embryo ◽  
Mouse Oocyte ◽  
Endogenous Retroviruses ◽  
Cdna Libraries ◽  
Alternative Promoters ◽  
Developmentally Regulated ◽  
Cell Stage ◽  
Stage Embryo

In dissecting the molecules and molecular mechanisms that control mammalian oocyte-to-embryo transition, we found abundant transcripts representing developmentally regulated ERVs (endogenous retroviruses) in mouse oocyte and two-cell stage embryo cDNA libraries. These retrotransposons can act as alternative promoters and first exons for diverse genes, synchronizing their expression. Heritable genetic change due to replication of these retrotransposons probably occurs specifically in oocytes and early embryos. ERVs are usually epigenetically silenced, through DNA methylation and chromatin-based mechanisms. Their activation and silencing indicates a change in the epigenetic state of the genome. The thousands of endogenous retro-elements in the mouse genome provides potential scope for large-scale co-ordinated epigenetic fluctuations and leads to the hypothesis that differential transposable element expression triggers sequential reprogramming of the embryonic genome during the oocyte-to-embryo transition.

scholarly journals Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes

2005 ◽  
Vol 34 (3) ◽  
pp. 889-908 ◽  
Author(s):  
S Bauersachs ◽  
S E Ulbrich ◽  
K Gross ◽  
S E M Schmidt ◽  
H H D Meyer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cdna Array ◽  
Transforming Growth Factor Β ◽  
Early Embryo ◽  
Oestrous Cycle ◽  
Cdna Libraries ◽  
Functional Changes ◽  
Retinoic Acid Signalling ◽  
Subtracted Cdna Libraries

The endometrium plays a central role among the reproductive tissues in the context of early embryo–maternal communication and pregnancy. It undergoes typical changes during the sexual/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages of the cycle – end of day 0 (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A combination of subtracted cDNA libraries and cDNA array hybridisation revealed 133 genes showing at least a 2-fold change of their mRNA abundance, 65 with higher levels at oestrus and 68 at dioestrus. Interestingly, genes were identified which showed differential expression between different uterine sections as well. The most prominent example was the UTMP (uterine milk protein) mRNA, which was markedly upregulated in the cranial part of the ipsilateral uterine horn at oestrus. A Gene Ontology classification of the genes with known function characterised the oestrus time by elevated expression of genes, for example related to cell adhesion, cell motility and extracellular matrix and the dioestrus time by higher expression of mRNAs encoding for a variety of enzymes and transport proteins, in particular ion channels. Searching in pathway databases and literature data-mining revealed physiological processes and signalling cascades, e.g. the transforming growth factor-β signalling pathway and retinoic acid signalling, which are potentially involved in the regulation of changes of the endometrium during the oestrous cycle.

scholarly journals Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 319-331 ◽  
Author(s):  
Stefan Bauersachs ◽  
Susanne E Ulbrich ◽  
Karin Gross ◽  
Susanne E M Schmidt ◽  
Heinrich H D Meyer ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Molecular Mechanisms ◽  
Cdna Array ◽  
Early Embryo ◽  
Cdna Libraries ◽  
Control Group ◽  
Regulation Of Transcription ◽  
Uterine Receptivity ◽  
Subtracted Cdna Libraries ◽  
Species Specific

The endometrium plays a central role among the reproductive tissues in the context of early embryo–maternal communication and pregnancy. This study investigated transcriptome profiles of endometrium samples from day 18 pregnant vs non-pregnant heifers to get insight into the molecular mechanisms involved in conditioning the endometrium for embryo attachment and implantation. Using a combination of subtracted cDNA libraries and cDNA array hybridisation, 109 mRNAs with at least twofold higher abundance in endometrium of pregnant animals and 70 mRNAs with higher levels in the control group were identified. Among the mRNAs with higher abundance in pregnant animals, at least 41 are already described as induced by interferons. In addition, transcript levels of many new candidate genes involved in the regulation of transcription, cell adhesion, modulation of the maternal immune system and endometrial remodelling were found to be increased. The different expression level was confirmed with real-time PCR for nine genes. Localisation of mRNA expression in the endometrium was shown byin situhybridisation forAGRN,LGALS3BP,LGALS9,USP18,PARP12andBST2. A comparison with similar studies in humans, mice, and revealed species-specific and common molecular markers of uterine receptivity.

Regulation of desmocollin transcription in mouse preimplantation embryos

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 743-753 ◽  
Author(s):  
J.E. Collins ◽  
J.E. Lorimer ◽  
D.R. Garrod ◽  
S.C. Pidsley ◽  
R.S. Buxton ◽  
...  
Keyword(s):  
Protein Expression ◽  
Molecular Mechanisms ◽  
Inner Cell Mass ◽  
Splice Variants ◽  
Cell Mass ◽  
Cumulus Cells ◽  
Early Embryo ◽  
Preimplantation Embryos ◽  
Cell Stage ◽  
Cleavage Stages

The molecular mechanisms regulating the biogenesis of the first desmosomes to form during mouse embryogenesis have been studied. A sensitive modification of a reverse transcriptase-cDNA amplification procedure has been used to detect transcripts of the desmosomal adhesive cadherin, desmocollin. Sequencing of cDNA amplification products confirmed that two splice variants, a and b, of the DSC2 gene are transcribed coordinately. Transcripts were identified in unfertilized eggs and cumulus cells and in cleavage stages up to the early 8-cell stage, were never detected in compact 8-cell embryos, but were evident again either from the 16-cell morula or very early blastocyst (approx 32-cells) stages onwards. These two phases of transcript detection indicate DSC2 is encoded by maternal and embryonic genomes. Previously, we have shown that desmocollin protein synthesis is undetectable in eggs and cleavage stages but initiates at the early blastocyst stage when desmocollin localises at, and appears to regulate assembly of, nascent desmosomes that form in the trophectoderm but not in the inner cell mass (Fleming, T. P., Garrod, D. R. and Elsmore, A. J. (1991), Development 112, 527–539). Maternal DSC2 mRNA is therefore not translated and presumably is inherited by blastomeres before complete degradation. Our results suggest, however, that initiation of embryonic DSC2 transcription regulates desmocollin protein expression and thereby desmosome formation. Moreover, data from blastocyst single cell analyses suggest that embryonic DSC2 transcription is specific to the trophectoderm lineage. Inhibition of E-cadherin-mediated cell-cell adhesion did not influence the timing of DSC2 embryonic transcription and protein expression. However, isolation and culture of inner cell masses induced an increase in the amount of DSC2 mRNA and protein detected. Taken together, these results suggest that the presence of a contact-free cell surface activates DSC2 transcription in the mouse early embryo.

scholarly journals β-Catenin is essential for patterning the maternally specified animal-vegetal axis in the sea urchin embryo

1998 ◽  
Vol 95 (16) ◽  
pp. 9343-9348 ◽  
Author(s):  
Athula H. Wikramanayake ◽  
Ling Huang ◽  
William H. Klein
Keyword(s):  
Sea Urchin ◽  
Molecular Mechanisms ◽  
Early Embryo ◽  
Cell Fates ◽  
Cell Stage ◽  
Signal Transduction Cascade ◽  
Sea Urchin Embryos ◽  
Sea Urchin Embryo ◽  
Vegetal Pole ◽  
Vegetal Cell

In sea urchin embryos, the animal-vegetal axis is specified during oogenesis. After fertilization, this axis is patterned to produce five distinct territories by the 60-cell stage. Territorial specification is thought to occur by a signal transduction cascade that is initiated by the large micromeres located at the vegetal pole. The molecular mechanisms that mediate the specification events along the animal–vegetal axis in sea urchin embryos are largely unknown. Nuclear β-catenin is seen in vegetal cells of the early embryo, suggesting that this protein plays a role in specifying vegetal cell fates. Here, we test this hypothesis and show that β-catenin is necessary for vegetal plate specification and is also sufficient for endoderm formation. In addition, we show that β-catenin has pronounced effects on animal blastomeres and is critical for specification of aboral ectoderm and for ectoderm patterning, presumably via a noncell-autonomous mechanism. These results support a model in which a Wnt-like signal released by vegetal cells patterns the early embryo along the animal–vegetal axis. Our results also reveal similarities between the sea urchin animal–vegetal axis and the vertebrate dorsal–ventral axis, suggesting that these axes share a common evolutionary origin.

scholarly journals PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo

2014 ◽  
Vol 205 (4) ◽  
pp. 447-455 ◽  
Author(s):  
Laura Benkemoun ◽  
Catherine Descoteaux ◽  
Nicolas T. Chartier ◽  
Lionel Pintard ◽  
Jean-Claude Labbé
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Cycle Duration ◽  
Cell Stage ◽  
C Elegans ◽  
Stage Embryo ◽  
Regulation Of Cell Cycle

Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division.

scholarly journals The Aryl Hydrocarbon Receptor Promotes Differentiation During Mouse Preimplantational Embryo Development

2020 ◽  
Author(s):  
Ana Nacarino-Palma ◽  
Jaime M. Merino ◽  
Pedro M. Fernández-Salguero
Keyword(s):  
Embryo Development ◽  
Molecular Mechanisms ◽  
Inner Cell Mass ◽  
Intracellular Localization ◽  
Cell Mass ◽  
Early Embryo ◽  
Mitochondrial Activity ◽  
Differentiation Markers ◽  
Cell Stage ◽  
Pluripotency Factors

ABSTRACTMammalian embryogenesis is a complex process controlled by transcription factors that dynamically regulate the balance between pluripotency and differentiation. Transcription factor AhR is known to regulate Oct4/Pou5f1 and Nanog, both essential genes in pluripotency, stemness and early embryo development. Yet, the molecular mechanisms controlling Oct4/Pou5f1 and Nanog during embryo development remain largely unidentified. Here, we show that AhR is required for proper embryo differentiation by regulating pluripotency factors and by maintaining adequate metabolic activity. AhR lacking embryos (AhR-/-) showed a more pluripotent phenotype characterized by a delayed expression of differentiation markers of the first and second cell divisions. Accordingly, central pluripotency factors OCT4/POU5F1, NANOG, and SOX2 were overexpressed in AhR-/- embryos at initial developmental stages. An altered intracellular localization of these factors was observed in absence of AhR and, importantly, OCT4 had an opposite expression pattern with respect to AhR from the 2-cell stage to blastocyst, suggesting a negative regulatory mechanism of OCT4/POU5F by AhR. Hippo signalling, rather than being repressed, was upregulated in very early AhR-/- embryos, possibly contributing to their undifferentiation at later stages. Consistently, AhR-null blastocysts overexpressed the early marker of inner cell mass (ICM) differentiation Sox17 whereas downregulated extraembryonic differentiation-driving genes Cdx2 and Gata3. Moreover, the persistent pluripotent phenotype of AhR-/- embryos was supported by an enhanced glycolytic metabolism and a reduction in mitochondrial activity. We propose that AhR is a regulator of pluripotency and differentiation in early mouse embryogenesis and that its deficiency may underline the reduced viability and increased resorptions of AhR-null mice.

scholarly journals HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Nature ◽  
2021 ◽  
Author(s):  
Fides Zenk ◽  
Yinxiu Zhan ◽  
Pavel Kos ◽  
Eva Löser ◽  
Nazerke Atinbayeva ◽  
...  
Keyword(s):  
Genome Organization ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Early Embryo ◽  
Heterochromatin Protein ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Genome Reorganization

AbstractFundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.

scholarly journals EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhao ◽  
Alan Blayney ◽  
Xiaorong Liu ◽  
Lauren Gandy ◽  
Weihua Jin ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Cancer Drug ◽  
Dynamic Interactions ◽  
Cancer Drug Discovery ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Cancerous Cells

AbstractEpigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG’s anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

scholarly journals Steroidal Regulation of Oviductal microRNAs Is Associated with microRNA-Processing in Beef Cows

2021 ◽  
Vol 22 (2) ◽  
pp. 953
Author(s):  
Angela Maria Gonella-Diaza ◽  
Everton Lopes ◽  
Kauê Ribeiro da Silva ◽  
Ricardo Perecin Nociti ◽  
Gabriella Mamede Andrade ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Sex Steroids ◽  
Molecular Mechanisms ◽  
Beef Cows ◽  
Early Embryo ◽  
Preovulatory Follicle ◽  
Large Follicle ◽  
Specific Manner ◽  
Microrna Processing ◽  
Small Follicle

Information on molecular mechanisms through which sex-steroids regulate oviductal function to support early embryo development is lacking. Here, we hypothesized that the periovulatory endocrine milieu affects the miRNA processing machinery and miRNA expression in bovine oviductal tissues. Growth of the preovulatory follicle was controlled to obtain cows that ovulated a small follicle (SF) and subsequently bore a small corpus luteum (CL; SF-SCL) or a large follicle (LF) and large CL (LF-LCL). These groups differed in the periovulatory plasmatic sex-steroid’s concentrations. Ampulla and isthmus samples were collected on day four of the estrous cycle. Abundance of DROSHA, DICER1, and AGO4 transcripts was greater in the ampulla than the isthmus. In the ampulla, transcription of these genes was greater for the SF-SCL group, while the opposite was observed in the isthmus. The expression of the 88 most abundant miRNAs and 14 miRNAs in the ampulla and 34 miRNAs in isthmus were differentially expressed between LF-LCL and SF-SCL groups. Integration of transcriptomic and miRNA data and molecular pathways enrichment showed that important pathways were inhibited in the SF-SCL group due to miRNA control. In conclusion, the endocrine milieu affects the miRNA expression in the bovine oviduct in a region-specific manner.

scholarly journals Integrative cBioPortal Analysis Revealed Molecular Mechanisms That Regulate EGFR-PI3K-AKT-mTOR Pathway in Diffuse Gliomas of the Brain

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3247
Author(s):  
Petar Brlek ◽  
Anja Kafka ◽  
Anja Bukovac ◽  
Nives Pećina-Šlaus
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Total Sample ◽  
Mtor Signaling ◽  
Biological Behavior ◽  
Mrna Transcription ◽  
Diffuse Gliomas ◽  
New Treatment ◽  
Using Data

Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior and a lack of effective treatment methods. Despite new molecular findings, the differences between pathohistological types still require better understanding. In this in silico analysis, we investigated AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 as participants of EGFR-PI3K-AKT-mTOR signaling using data from the publicly available cBioPortal platform. Integrative large-scale analyses investigated changes in copy number aberrations (CNA), methylation, mRNA transcription and protein expression within 751 samples of diffuse astrocytomas, anaplastic astrocytomas and glioblastomas. The study showed a significant percentage of CNA in PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%) in the total sample. Comprehensive statistical analyses show how genomics and epigenomics affect the expression of examined genes differently across various pathohistological types and grades, suggesting that genes AKT3, CHUK and PTEN behave like tumor suppressors, while AKT1, AKT2, EGFR, and PIK3AP1 show oncogenic behavior and are involved in enhanced activity of the EGFR-PI3K-AKT-mTOR signaling pathway. Our findings contribute to the knowledge of the molecular differences between pathohistological types and ultimately offer the possibility of new treatment targets and personalized therapies in patients with diffuse gliomas.

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