Disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes during embryogenesis

Development ◽  
1998 ◽  
Vol 125 (8) ◽  
pp. 1553-1560 ◽  
Author(s):  
Y. Obata ◽  
T. Kaneko-Ishino ◽  
T. Koide ◽  
Y. Takai ◽  
T. Ueda ◽  
...  
Keyword(s):  
Epigenetic Modifications ◽  
The Other ◽  
Imprinted Genes ◽  
Oocyte Growth ◽  
Parthenogenetic Development ◽  
Crucial Effect ◽  
H19 Gene ◽  
Parthenogenetic Embryos

Parthenogenetic embryos, which contained one genome from a neonate-derived non-growing oocyte and the other from a fully grown oocyte, developed to day 13.5 of gestation in mice, 3 days longer than previously recorded for parthenogenetic development. To investigate the hypothesis that disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes and this parthenogenetic phenotype, we have examined Peg1/Mest, Igf2, Peg3, Snrpn, H19, Igf2r and excess p57KIP2. We show that paternally expressed genes, Peg1/Mest, Peg3 and Snrpn, are expressed in the parthenotes, presumably due to a lack of maternal epigenetic modifications during oocyte growth. In contrast, the expression of Igf2, which is repressed in a competitive manner by transcription of the H19 gene, was very low. Furthermore, we show that the maternally expressed Igf2r and p57KIP2 genes were repressed in the alleles of the non-growing oocyte indicating maternal modifications during oocyte growth are necessary for its expression. Thus, our results show that primary imprinting during oocyte growth exhibits a crucial effect on both the expression and repression of maternal alleles during embryogenesis.

scholarly journals 171 NORMAL REPROGRAMMING OF IMPRINTING IN PARTHENOGENETIC FEMALE GERM CELLS

2005 ◽  
Vol 17 (2) ◽  
pp. 236
Author(s):  
T. Horii ◽  
Y. Nagao ◽  
M. Kimura ◽  
I. Hatada
Keyword(s):  
Germ Cells ◽  
Restriction Analysis ◽  
Primordial Germ Cells ◽  
Fluorescent Microscopy ◽  
Embryonic Stem ◽  
Postnatal Growth ◽  
The Other ◽  
Imprinted Genes ◽  
Host Embryo ◽  
Parthenogenetic Embryos

Mammalian parthenotes cannot develop normally to term. Mouse parthenogenetic embryos die by Day 10 of gestation. On the other hand, viable parthenogenetic chimeras were produced by normal host embryos, although parthenogenetic cells were observed in a limited number of tissues and organs and, even in these instances, their contribution was substantially reduced. This can be explained by the aberrant expressions of imprinted genes in parthenogenetic cells. In female mice, erasure of imprints occurs around the time that primordial germ cells enter the gonad, and establishment of imprints occurs in the postnatal growth phase of oogenesis. In this study, we investigated whether aberrant imprints in parthenogenetic embryonic stem (PgES) cells can be erased through the germline. Diploid parthenogenetic embryos were produced by activation of (CBA × C57BL/6-EGFP) F1 mouse superovulated unfertilized oocytes by exposure to Sr2+ and cytochalasin B. Ten parthenogenetic blastocysts were plated and three PgES cell lines were isolated. Chimeras were made by injecting 10–15 PgES cells into ICR(CD-1) mouse blastocysts. Chimeras and chimeric tissues were detected by fluorescent microscopy. In all, 173 chimeric blastocysts were transferred to 9 recipient females, and 101 live pups containing 9 female and 21 male chimeras were born. No significant growth retardation was apparent in PgES chimeras, irrespective of their degree of chimerism. In 5 male chimeras killed at 1 day postpartum (dpp), PgES cells showed a restricted tissue contribution. The contribution to lung, liver, and intestine was considerably lower than in the other tissues such as brain, heart, spleen, and kidney. PgES derived or host embryo derived non-growing oocytes were isolated from dissociated ovaries of female chimeras at 1 dpp under fluorescent microscopy. Methylation imprints in non-growing oocytes were analyzed for maternally methylated imprinted genes Peg1, Snrpn, and Igf2r by the combined bisulfite restriction analysis (COBRA). In normal oocytes, imprints are expected to be erased and these genes are unmethylated at this stage. We observed that these genes were unmethylated in both PgES derived and host embryo derived non-growing oocytes. These results suggest that aberrant imprints in PgES cells can also be erased normally through the germline.

scholarly journals Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term

Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 481-488 ◽  
Author(s):  
Qiong Wu ◽  
Takuya Kumagai ◽  
Manabu Kawahara ◽  
Hidehiko Ogawa ◽  
Hitoshi Hiura ◽  
...  
Keyword(s):  
Transcription Unit ◽  
Imprinted Genes ◽  
Wild Type ◽  
Expression Levels ◽  
Paternal Contribution ◽  
Parthenogenetic Development ◽  
Normal Expression ◽  
Regulated Expression ◽  
Insight Into ◽  
Parthenogenetic Embryos

Mouse parthenogenetic embryos (PEs) are developmentally arrested until embryo day (E) 9.5 because of genomic imprinting. However, we have shown that embryos containing genomes from non-growing (ng) and fully grown (fg) oocytes, i.e. ngwt/fgwt PE (wt, wild type), developed to E13.5. Moreover, parthenogenetic development could be extended to term by further regulation of Igf2 and H19 expression using mice with deletion of the H19 transcription unit (H19Δ13) together with its differentially unit (DMR). To gain an insight into the extended development of the parthenotes to term, we have here investigated the expression levels of paternally imprinted genes in ngH19Δ13/fgwt PE throughout their development. In ngH19Δ13/fgwt Pes that died soon after recovery, the expression of Igf2 and H19 was restored to the appropriate levels except for low Igf2 expression in the liver after E15.5. Further, the paternally expressed Dlk1 and Dio3 were repressed, while the expression levels of the maternal Gtl2 and Mirg were twice those of the controls. However, the above-mentioned four genes showed almost normal expression in the surviving ngH19Δ13/fgwt PEs. The methylation analysis revealed that the intragenic DMR of the Dlk1-Gtl2 domain was hypermethylated in the ngH19Δ13/fgwt PEs that survived, but not in the PEs that died soon after recovery. The present study suggests that two sets of co-ordinately regulated but oppositely expressed genes, Igf2-H19 and Dlk1-Gtl2, act as a critical barrier to parthenogenetic development in order to render a paternal contribution obligatory for descendants in mammals.

Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse

1996 ◽  
Vol 13 (1) ◽  
pp. 91-94 ◽  
Author(s):  
Tomohiro Kono ◽  
Yayoi Obata ◽  
Tomomi Yoshimzu ◽  
Tatsuo Nakahara ◽  
John Carroll
Keyword(s):  
Epigenetic Modifications ◽  
Oocyte Growth ◽  
Parthenogenetic Development

Genetic modification for bimaternal embryo development

2009 ◽  
Vol 21 (1) ◽  
pp. 31 ◽  
Author(s):  
Tomohiro Kono
Keyword(s):  
Embryo Development ◽  
Genetic Modification ◽  
Direct Evidence ◽  
Epigenetic Modification ◽  
Growth Period ◽  
Epigenetic Modifications ◽  
Imprinted Genes ◽  
Mammalian Development ◽  
Oocyte Growth ◽  
Paternal Contribution

Full mammalian development typically requires genomes from both the oocyte and spermatozoon. Biparental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis; that is, a maternal methylation imprint imposed during the oocyte growth period and a paternal methylation imprint imposed in pregonadal gonocytes. This leads to unequivalent expression of imprinted genes from the maternal and paternal alleles in embryos and individuals. It is possible to hypothesise that the maternal methylation imprint is necessary to prevent parthenogenesis, which extinguishes the opportunity for having descendents, whereas the paternal methylation imprint prevents parthenogenesis, ensuring that a paternal contribution is obligatory for any descendants. To date, there are several lines of direct evidence that the epigenetic modifications that occur during oocyte growth have a decisive effect on mammalian development. Using bimaternal embryos with two sets of maternal genomes, the present paper illustrates how parental methylation imprints are an obstacle to the progression of parthenogenesis.

scholarly journals ZFP57 dictates allelic expression switch of target imprinted genes

2021 ◽  
Vol 118 (5) ◽  
pp. e2005377118
Author(s):  
Weijun Jiang ◽  
Jiajia Shi ◽  
Jingjie Zhao ◽  
Qiu Wang ◽  
Dan Cong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mouse Embryos ◽  
The Other ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Parent Of Origin

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

Imprinting analysis in the Acrodysplasia region of mouse chromosome 12

2009 ◽  
Vol 30 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Erin N. McMurray ◽  
Eric D. Rogers ◽  
Jennifer V. Schmidt
Keyword(s):  
Mouse Chromosome ◽  
Genomic Imprinting ◽  
Critical Region ◽  
The Other ◽  
Chromosome 12 ◽  
Imprinted Genes ◽  
Skeletal Abnormalities ◽  
Mouse Mutation ◽  
Parent Of Origin

The insertional mouse mutation Adp (Acrodysplasia) confers a parent-of-origin developmental phenotype, with animals inheriting the mutation from their father showing skeletal abnormalities, whereas those inheriting the mutation from their mother are normal. This parental-specific phenotype, along with mapping of the insertion to a region of chromosome 12 proposed to contain imprinted genes, suggested that disruption of genomic imprinting might underlie the Adp phenotype. Genomic imprinting is the process by which autosomal genes are epigenetically silenced on one of the two parental alleles; imprinting mutation phenotypes manifest after inheritance from one parent but not the other. Imprinted genes typically occur in dense clusters that contain few non-imprinted genes and therefore representative genes from the Adp critical region could be assayed to identify any imprinted domains. None of the genes analysed were found to be imprinted, however, suggesting that other explanations for the Adp phenotype must be considered.

Defects in the allocation of cells to the inner cell mass and trophectoderm of parthenogenetic mouse blastocysts

1996 ◽  
Vol 8 (8) ◽  
pp. 1193 ◽  
Author(s):  
B Mognetti ◽  
D Sakkas
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Substantial Reduction ◽  
Cell Lineage ◽  
Blastocyst Stage ◽  
Trophectoderm Cells ◽  
Parthenogenetic Development ◽  
Preimplantation Stage ◽  
Parthenogenetic Mouse Embryos ◽  
Parthenogenetic Embryos

Diploid parthenogenetic mouse embryos (which possess two maternally-derived genomes) can develop only as far as the 25-somite stage when transferred in utero and exhibit a substantial reduction in trophoblast tissue. The loss of cultured parthenogenetic embryos during postimplantation indicates that a defect in cell lineage may be evident as early as the blastocyst stage. The possibility that a defect may already be reflected at the preimplantation stage was investigated by examining the allocation of cells to the trophectoderm (trophoblast progenitor cells) and the inner cell mass of haploid and diploid parthenogenetic mouse blastocysts. Utilizing a differential labelling technique for counting cells, diploid parthenogenetic blastocysts were found to have fewer inner cell mass cells and trophectoderm cells than their haploid counterparts and normal blastocysts. In addition, both haploid and diploid parthenogenetic blastocysts had a lower inner cell mass: trophectoderm ratio than normal blastocysts. Thus, the relatively poor development of the trophectoderm lineage at the postimplantation stage is not reflected by a reduction in its allotment of cells at its first appearance. Nevertheless, the findings indicate that parthenogenetic development is already compromised at the blastocyst stage, and provide evidence that the expression of imprinted genes has significance for the development of the embryo at the preimplantation stage.

scholarly journals Evolution of imprinting via lineage-specific insertion of retroviral promoters

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aaron B. Bogutz ◽  
Julie Brind’Amour ◽  
Hisato Kobayashi ◽  
Kristoffer N. Jensen ◽  
Kazuhiko Nakabayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Endogenous Retroviruses ◽  
The Other ◽  
Imprinted Genes ◽  
Evolutionary Mechanism ◽  
Female Mice ◽  
Parental Allele ◽  
Species Specific ◽  
Human Specific

AbstractImprinted genes are expressed from a single parental allele, with the other allele often silenced by DNA methylation (DNAme) established in the germline. While species-specific imprinted orthologues have been documented, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a transcription-guided manner. Here we show that oocyte transcription initiating in lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme establishment at 4/6 mouse-specific and 17/110 human-specific imprinted gDMRs. The latter are divided into Catarrhini- or Hominoidea-specific gDMRs embedded within transcripts initiating in ERVs specific to these primate lineages. Strikingly, imprinting of the maternally methylated genes Impact and Slc38a4 was lost in the offspring of female mice harboring deletions of the relevant murine-specific ERVs upstream of these genes. Our work reveals an evolutionary mechanism whereby maternally silenced genes arise from biallelically expressed progenitors.

scholarly journals Alterations in epigenetic modifications during oocyte growth in mice

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Shun-ichiro Kageyama ◽  
Honglin Liu ◽  
Naoto Kaneko ◽  
Masatoshi Ooga ◽  
Masao Nagata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Epigenetic Modification ◽  
Germinal Vesicle ◽  
Epigenetic Modifications ◽  
Condensed Chromatin ◽  
Rt Pcr ◽  
Oocyte Growth ◽  
Lysine Residues ◽  
Signal Intensities

During oocyte growth, chromatin structure is altered globally and gene expression is silenced. To investigate the involvement of epigenetic modifications in the regulation of these phenomena, changes in global DNA methylation and in various histone modifications, i.e. acetylation of H3K9, H3K18, H4K5, and H4K12, and methylation of H3K4 and H3K9, were examined during the growth of mouse oocytes. Immunocytochemical analysis revealed that the signal intensities of all these modifications increased during growth and that fully grown, germinal vesicle (GV)-stage oocytes showed the most modifications. Since acetylation of most of the lysine residues on histones and methylation of H3K4 are associated with active gene expression, the increased levels of these modifications do not seem to be associated with gene silencing in GV-stage oocytes. Given that there are two types of GV-stage oocytes with different chromatin configurations and transcriptional activities, the epigenetic modification statuses of these two types were compared. The levels of all the epigenetic modifications examined were higher in the SN(surrounded nucleolus)-type oocytes, in which highly condensed chromatin is concentrated in the area around the nucleolus and gene expression is silenced than in the NSN(not surrounded nucleolus)-type oocytes, in which less-condensed chromatin does not surround the nucleolus and gene expression is active. In addition, the expression levels of various enzymes that catalyze histone modifications were shown by RT-PCR to increase with oocyte growth. Taken together, the results show that all of the epigenetic modifications increased in a concerted manner during oocyte growth, and suggest that these increases are not associated with gene expression.

Genomic imprinting, development and disease—is pre-eclampsia caused by a maternally imprinted gene?

1998 ◽  
Vol 10 (1) ◽  
pp. 23 ◽  
Author(s):  
Jennifer A. Marshall Graves
Keyword(s):  
Genomic Imprinting ◽  
Fetal Development ◽  
Mutant Gene ◽  
The Other ◽  
Paternal Allele ◽  
Imprinted Genes ◽  
Maternal Expression ◽  
Mutant Genes ◽  
Normal Placenta ◽  
Mode Of Inheritance

Several genes in conserved clusters are expressed from only the maternal or the paternal allele. The other allele has been genetically silenced (‘imprinted’) by its passage through one sex. Many known imprinted genes have effects on embryonic or trophoblast growth or fetal development, and mutation or loss of the single active copy causes diseases such as Prader–Willi, Angelmann and Beckwith–Wiederman syndromes. Imprinted genes show an unusual mode of inheritance, since mutant genes have an effect on the phenotype only if they come from the parent from which they are expressed. This may explain some conditions which appear to be heritable but show an inconsistant pattern in affected families. Of particular interest is pre-eclampsia/eclampsia, the most serious complication of pregnancy, which has some features suggesting that it results from fetal expression of the mutant gene, but others which imply it results from maternal expression. This could be resolved by proposing that the condition is due to mutation in a paternally imprinted, maternally active gene which must be expressed by the fetus in order to establish a normal placenta in the first pregnancy.

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