Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nuf2 is required for chromosome segregation during mouse oocyte meiotic maturation.

ABSTRACT: Nuf2 plays an important role in kinetochore-microtubule attachment and thus is involved in regulation of the spindle assembly checkpoint in mitosis. In this study, we examined the localization and function of Nuf2 during mouse oocyte meiotic maturation. Myc6-Nuf2 mRNA injection and immunofluorescent staining showed that Nuf2 localized to kinetochores from germinal vesicle breakdown to metaphase I stages, while it disappeared from the kinetochores at the anaphase I stage, but relocated to kinetochores at the MII stage. Overexpression of Nuf2 caused defective spindles, misaligned chromosomes, and activated spindle assembly checkpoint, and thus inhibited chromosome segregation and metaphase-anaphase transition in oocyte meiosis. Conversely, precocious polar body extrusion was observed in the presence of misaligned chromosomes and abnormal spindle formation in Nuf2 knock-down oocytes, causing aneuploidy. Our data suggest that Nuf2 is a critical regulator of meiotic cell cycle progression in mammalian oocytes.

SUBMITTER: Zhang T

PROVIDER: S-EPMC4613995 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

PHF1 is required for chromosome alignment and asymmetric division during mouse meiotic oocyte maturation.

Project description:In recent years, the etiological study of oocyte maturation failure and other mechanisms of early embryonic development has gradually advanced. However, while some achievements have been made in this field, the intrinsic mechanisms underlying disordered oocyte maturation remain unclear. Polycomb group proteins (PcG) are a family of proteins that are involved in the epigenetic silencing of genes. Many members of this family are reportedly involved in mammalian oocyte maturation and early embryonic development. PHD finger protein 1 (PHF1) is a core member of the polycomblike group of proteins, although its role in oocyte maturation and early embryonic development are unknown. A previous study by our group using single cell transcriptome analysis and high-throughput technology revealed that PHF1 mRNA was elevated in the human oocyte and the early preimplantation embryo. This suggests that PHF1 may play an important role in oocyte maturation and early embryonic development. In the present study, we aimed to reveal the biological function of PHF1 in mouse oocyte maturation and illuminate its regulatory mechanisms. We report here, for the first time, that PHF1 is necessary for the accurate alignment of chromosomes and oocyte euploidy, as well for the regulation of the asymmetric division of oocytes in mouse. The results of the present study may have the potential to provide a new research direction of human oocyte maturation disorder and early embryonic development block. These results may also provide new diagnosis or treatment strategies for clinical patients.

| S-EPMC6342080 | biostudies-literature

p38? MAPK is a MTOC-associated protein regulating spindle assembly, spindle length and accurate chromosome segregation during mouse oocyte meiotic maturation.

Project description:P38?MAPK (p38?) is usually activated in response to various stresses and plays a role in the inhibition of cell proliferation and tumor progression, but little is known about its roles in meiotic spindle assembly. In this study, we characterized the dynamic localization of p38? and explored its function in mouse oocyte meiotic maturation. P38? specifically colocalized with ?-tubulin and Plk1 at the center of MTOCs and spindle poles. Depletion of p38? by specific morpholino injection resulted in severely defective spindles and misaligned chromosomes probably via MK2 dephosphorylation. Notably, depletion of p38? led to significant spindle pole defects, spindle elongation, non-tethered kinetochore microtubules and increased microtubule tension. The disruption of spindle stability was coupled with decreased ?-tubulin and Plk1 at MTOCs. Overexpression of Eg5, a conserved motor protein, also caused spindle elongation and its morpholino injection almost completely rescued spindle elongation caused by p38? depletion. In addition, p38?-depletion decreased BubR1 and interfered with spindle assembly checkpoint (SAC), which resulted in aneuploid oocytes. Together, these data indicate that p38? is an important component of MTOCs, which regulates spindle assembly and spindle length, as well as stabilizes the spindle and spindle poles. Perturbed SAC and abnormal microtubule tension may be responsible for the misaligned chromosomes and high aneuploidy in p38?-depleted mouse oocytes.

| S-EPMC3055197 | biostudies-literature

FKBP25 Regulates Meiotic Apparatus During Mouse Oocyte Maturation.

Project description:FK506 binding proteins 25 (FKBP25) has been shown to function in ribosome biogenesis, chromatin organization, and microtubule stability in mitosis. However, the role of FKBP25 in oocyte maturation has not been investigated. Here, we report that oocytes with FKBP25 depletion display abnormal spindle assembly and chromosomes alignment, with defective kinetochore-microtubule attachment. Consistent with this finding, aneuploidy incidence is also elevated in oocytes depleted of FKBP25. Importantly, FKBP25 protein level in old oocytes is significantly reduced, and ectopic expression of FKBP25 could partly rescue the aging-associated meiotic defects. In addition, by employing site-specific mutagenesis, we identify that serine 163 is a major, if not unique, phosphorylation site modulating the action of FKBP25 on meiotic maturation. In summary, our data indicate that FKBP25 is a pivotal factor for determining oocyte quality, and may mediate the effects of maternal aging on female reproduction.

| S-EPMC7859338 | biostudies-literature

TBP dynamics during mouse oocyte meiotic maturation and early embryo development.

Project description:To maintain cell lineage, cells develop a mechanism which can transmit the gene activity information to the daughter cells. In mitosis, TBP (TATA-binding protein), a transcription factor which belongs to TFIID was associated with M phase chromosomes and was proved to be a bookmark for cellular memory. Although previous work showed that TBP was dispensable for mouse oocyte maturation and early embryo development, exogenous TBP protein was detected in the nuclear of oocytes and early embryos. It is still unknown whether exogenous TBP can associate with condensed chromosomes during meiosis and mouse early embryo development. In present study by the injection of GFP-tagged TBP mRNA we for the first time investigated TBP dynamics in mouse early embryos and confirmed its localization pattern in oocytes. The exogenous TBP enriched at germinal vesicle at GV stage but disappeared from the chromosomes after GVBD. Moreover, exogenous TBP was still dispersed from the chromosomes of somatic donor nuclear in oocytes by nuclear transfer (NT), further proving that oocyte has some mechanism to remove TBP. During mouse embryo development, the exogenous TBP was removed from the chromosomes of M phase zygotes, but was found to express weakly at the M phase of 2-cell. Moreover, in the blastocyst TBP was also detected at the M phase chromosomes. Overexpression of TBP caused the failure of oocyte maturation and embryo development. Our results supported the idea that TBP might be a marker for transmitting cellular memory to daughter cells.

| S-EPMC3561223 | biostudies-literature

Histone deacetylase 2 (HDAC2) regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse.

Project description:Changes in histone acetylation occur during oocyte development and maturation, but the role of specific histone deacetylases in these processes is poorly defined. We report here that mice harboring Hdac1(-/+)/Hdac2(-/-) or Hdac2(-/-) oocytes are infertile or sub-fertile, respectively. Depleting maternal HDAC2 results in hyperacetylation of H4K16 as determined by immunocytochemistry--normal deacetylation of other lysine residues of histone H3 or H4 is observed--and defective chromosome condensation and segregation during oocyte maturation occurs in a sub-population of oocytes. The resulting increased incidence of aneuploidy likely accounts for the observed sub-fertility of mice harboring Hdac2(-/-) oocytes. The infertility of mice harboring Hdac1(-/+)/Hdac2(-/-)oocytes is attributed to failure of those few eggs that properly mature to metaphase II to initiate DNA replication following fertilization. The increased amount of acetylated H4K16 likely impairs kinetochore function in oocytes lacking HDAC2 because kinetochores in mutant oocytes are less able to form cold-stable microtubule attachments and less CENP-A is located at the centromere. These results implicate HDAC2 as the major HDAC that regulates global histone acetylation during oocyte development and, furthermore, suggest HDAC2 is largely responsible for the deacetylation of H4K16 during maturation. In addition, the results provide additional support that histone deacetylation that occurs during oocyte maturation is critical for proper chromosome segregation.

| S-EPMC3597510 | biostudies-literature

Betaine is accumulated via transient choline dehydrogenase activation during mouse oocyte meiotic maturation.

Project description:Betaine (N,N,N-trimethylglycine) plays key roles in mouse eggs and preimplantation embryos first in a novel mechanism of cell volume regulation and second as a major methyl donor in blastocysts, but its origin is unknown. Here, we determined that endogenous betaine was present at low levels in germinal vesicle (GV) stage mouse oocytes before ovulation and reached high levels in the mature, ovulated egg. However, no betaine transport into oocytes was detected during meiotic maturation. Because betaine can be synthesized in mammalian cells via choline dehydrogenase (CHDH; EC 1.1.99.1), we assessed whether this enzyme was expressed and active. Chdh transcripts and CHDH protein were expressed in oocytes. No CHDH enzyme activity was detected in GV oocyte lysate, but CHDH became highly active during oocyte meiotic maturation. It was again inactive after fertilization. We then determined whether oocytes synthesized betaine and whether CHDH was required. Isolated maturing oocytes autonomously synthesized betaine in vitro in the presence of choline, whereas this failed to occur in Chdh-/- oocytes, directly demonstrating a requirement for CHDH for betaine accumulation in oocytes. Overall, betaine accumulation is a previously unsuspected physiological process during mouse oocyte meiotic maturation whose underlying mechanism is the transient activation of CHDH.

| S-EPMC5566531 | biostudies-literature

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation.

Project description:SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293-PDHE1α mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age-associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality.

| S-EPMC6052465 | biostudies-literature

TGN38 is required for the metaphase I/anaphase I transition and asymmetric cell division during mouse oocyte meiotic maturation.

Project description:The cellular functions of the trans-Golgi network protein TGN38 remain unknown. In this research, we studied the expression, localization and functions of TGN38 in the meiotic maturation of mouse oocytes. TGN38 was expressed at every stage of oocyte meiotic maturation and colocalized with γ-tubulin at metaphase I and metaphase II. The spindle microtubule disturbing agents nocodazole and taxol did not affect the colocalization of TGN38 and γ-tubulin. Depletion of TGN38 with specific siRNAs resulted in increased metaphase I arrest, accompanied with spindle assembly checkpoint activation and decreased first polar extrusion (PB1). In the oocytes that had extruded the PB1 after the depletion of TGN38, symmetric division occurred, leading to the production of 2 similarly sized cells. Moreover, the peripheral migration of metaphase I spindle and actin cap formation were impaired in TGN38-depleted oocytes. Our data suggest that TGN38 may regulate the metaphase I/anaphase I transition and asymmetric cell division in mouse oocytes.

| S-EPMC4613595 | biostudies-other

Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.

Project description:In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1-3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.

| S-EPMC2765619 | biostudies-literature

EZH2 is required for mouse oocyte meiotic maturation by interacting with and stabilizing spindle assembly checkpoint protein BubRI.

Project description:Enhancer of zeste homolog 2 (EZH2) trimethylates histone H3 Lys 27 and plays key roles in a variety of biological processes. Stability of spindle assembly checkpoint protein BubR1 is essential for mitosis in somatic cells and for meiosis in oocytes. However, the role of EZH2 in oocyte meiotic maturation was unknown. Here, we presented a mechanism underlying EZH2 control of BubR1 stability in the meiosis of mouse oocytes. We identified a methyltransferase activity-independent function of EZH2 by demonstrating that EZH2 regulates spindle assembly and the polar body I extrusion. EZH2 was increased with the oocyte progression from GVBD to MII, while EZH2 was concentrated on the chromosomes. Interestingly, inhibition of EZH2 methyltranferase activity by DZNep or GSK343 did not affect oocyte meiotic maturation. However, depletion of EZH2 by morpholino led to chromosome misalignment and abnormal spindle assembly. Furthermore, ectopic expression of EZH2 led to oocyte meiotic maturation arrested at the MI stage followed by chromosome misalignment and aneuploidy. Mechanistically, EZH2 directly interacted with and stabilized BubR1, an effect driving EZH2 into the concert of meiosis regulation. Collectively, we provided a paradigm that EZH2 is required for mouse oocyte meiotic maturation.

| S-EPMC5027481 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data