Nejvíce citovaný článek - PubMed ID 8398131
Successful reproduction requires an oocyte competent to sustain early embryo development. By the end of oogenesis, the oocyte has entered a transcriptionally silenced state, the mechanisms and significance of which remain poorly understood. Histone H3.3, a histone H3 variant, has unique cell cycle-independent functions in chromatin structure and gene expression. Here, we have characterised the H3.3 chaperone Hira/Cabin1/Ubn1 complex, showing that loss of function of any of these subunits causes early embryogenesis failure in mouse. Transcriptome and nascent RNA analyses revealed that transcription is aberrantly silenced in mutant oocytes. Histone marks, including H3K4me3 and H3K9me3, are reduced and chromatin accessibility is impaired in Hira/Cabin1 mutants. Misregulated genes in mutant oocytes include Zscan4d, a two-cell specific gene involved in zygote genome activation. Overexpression of Zscan4 in the oocyte partially recapitulates the phenotypes of Hira mutants and Zscan4 knockdown in Cabin1 mutant oocytes partially restored their developmental potential, illustrating that temporal and spatial expression of Zscan4 is fine-tuned at the oocyte-to-embryo transition. Thus, the H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and embryogenesis, through modulating chromatin condensation and transcriptional quiescence.
- Klíčová slova
- Competent oocyte, Hira complex, Histone H3.3, Oocyte-to-embryo transition, Zygotic genome activation,
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- chromatin metabolismus MeSH
- embryonální vývoj genetika MeSH
- genový knockdown MeSH
- histonové chaperony genetika metabolismus MeSH
- histony metabolismus MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- oocyty růst a vývoj metabolismus MeSH
- oogeneze genetika MeSH
- proteiny buněčného cyklu genetika metabolismus MeSH
- signální transdukce genetika MeSH
- transkripční faktory genetika metabolismus MeSH
- zvířata MeSH
- zygota metabolismus MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- adaptorové proteiny signální transdukční MeSH
- Cabin1 protein, mouse MeSH Prohlížeč
- chromatin MeSH
- Hira protein, mouse MeSH Prohlížeč
- histonové chaperony MeSH
- histony MeSH
- proteiny buněčného cyklu MeSH
- transkripční faktory MeSH
- Zscan4d protein, mouse MeSH Prohlížeč
The onset of an early development is, in mammals, characterized by profound changes of multiple aspects of cellular morphology and behavior. These are including, but not limited to, fertilization and the merging of parental genomes with a subsequent transition from the meiotic into the mitotic cycle, followed by global changes of chromatin epigenetic modifications, a gradual decrease in cell size and the initiation of gene expression from the newly formed embryonic genome. Some of these important, and sometimes also dramatic, changes are executed within the period during which the gene transcription is globally silenced or not progressed, and the regulation of most cellular activities, including those mentioned above, relies on controlled translation. It is known that the blastomeres within an early embryo are prone to chromosome segregation errors, which might, when affecting a significant proportion of a cell within the embryo, compromise its further development. In this review, we discuss how the absence of transcription affects the transition from the oocyte to the embryo and what impact global transcriptional silencing might have on the basic cell cycle and chromosome segregation controlling mechanisms.
- Klíčová slova
- cell cycle, embryo, oocyte, transcriptional repression, translation,
- MeSH
- buněčný cyklus genetika MeSH
- chromatin genetika MeSH
- embryo savčí fyziologie MeSH
- embryonální vývoj genetika MeSH
- genetická transkripce genetika MeSH
- lidé MeSH
- segregace chromozomů genetika MeSH
- umlčování genů fyziologie MeSH
- vývojová regulace genové exprese genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chromatin MeSH
Granulosa cells (GCs) are somatic cells essential for establishing and maintaining bi-directional communication with the oocytes. This connection has a profound importance for the delivery of energy substrates, structural components and ions to the maturing oocyte through gap junctions. Cumulus cells, group of closely associated GCs, surround the oocyte and can diminished the effect of harmful environmental insults. Both GCs and oocytes prefer different energy substrates in their cellular metabolism: GCs are more glycolytic, whereas oocytes rely more on oxidative phosphorylation pathway. The interconnection of these cells is emphasized by the fact that GCs supply oocytes with intermediates produced in glycolysis. The number of GCs surrounding the oocyte and their age affect the energy status of oocytes. This review summarises available studies collaboration of cellular types in the ovarian follicle from the point of view of energy metabolism, signaling and protection of toxic insults. A deeper knowledge of the underlying mechanisms is crucial for better methods to prevent and treat infertility and to improve the technology of in vitro fertilization.
- MeSH
- antioxidancia metabolismus MeSH
- energetický metabolismus MeSH
- folikulární buňky účinky léků metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- metabolismus sacharidů MeSH
- nebezpečné látky toxicita MeSH
- oocyty růst a vývoj metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia MeSH
- nebezpečné látky MeSH
- reaktivní formy kyslíku MeSH
Nucleoli are the site of ribosomal RNA production and subunit assembly. In contrast to active nucleoli in somatic cells, where three basic sub-compartments can be observed, mammalian oocytes and early embryos contain atypical nucleoli termed "nucleolus-like bodies" or "nucleolus precursor bodies", respectively. Unlike their somatic counterparts, these structures are composed of dense homogenous fibrillar material and exhibit no polymerase activity. Irrespective of these unusual properties, they have been shown to be absolutely essential for embryonic development, as their microsurgical removal results in developmental arrest. Historically, nucleolus-like and nucleolus precursor bodies have been perceived as passive storage sites of nucleolar material, which is gradually utilized by embryos to construct fully functional nucleoli once they have activated their genome and have started to produce ribosomes. For decades, researchers have been trying to elucidate the composition of these organelles and provide the evidence for their repository role. However, only recently has it become clear that the function of these atypical nucleoli is altogether different, and rather than being involved in ribosome biogenesis, they participate in parental chromatin remodeling, and strikingly, the artificial introduction of a single NPB component is sufficient to rescue the developmental arrest elicited by the NPB removal. In this review, we will describe and summarize the experiments that led to the change in our understanding of these unique structures.
- Klíčová slova
- Oocyte, chromatin remodeling, embryo, nucleolus, ribosome,
- MeSH
- buněčné jadérko genetika metabolismus MeSH
- chromatin genetika metabolismus MeSH
- embryonální vývoj genetika MeSH
- lidé MeSH
- restrukturace chromatinu * MeSH
- ribozomy genetika metabolismus MeSH
- zárodečné buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chromatin MeSH
For somatic cell nuclear transfer cytoplasts from metaphase II, oocytes are exclusively used. However, it is evident that certain reprogramming activities are present in oocytes even at earlier stages of maturation. These activities are, however, only poorly characterised. The main reason for this is that even the intrinsic oocyte processes are insufficiently understood. The mammalian oocyte is a highly specialised cell that harbours many specific characteristics. One of these is its particularly large size when compared to somatic cells. As the oocyte enters the growth phase its volume, as well as the amount of material, increases considerably. Thus, it is clear that the oocyte must possess the machinery to accomplish this incredible material accumulation. When the growth phase is completed, the transcription ceases and the oocyte becomes transcriptionally inactive. In our study, we have used the model system of oocyte fusion (transcribing x non-transcribing germinal vesicle (GV) stage oocytes) as a substitute for a somatic cell nuclear transfer schemes where the somatic cell nucleus would be introduced into a cytoplast obtained from a GV stage oocyte. We wanted to determine if the fully grown GV stage oocyte could induce reprogramming of transcriptionally active transferred nucleus by suppressing this activity. In order to evaluate possible changes in transcriptional properties after nuclear transfer, we also investigated the mechanism of transcriptional silencing taking place when the oocyte reaches its full size as well as the fate of the components namely of the RNA polymerase II (Pol II) transcriptional and splicing machinery. Here, we show that while the Pol II is degraded in fully grown GV stage oocytes and the splicing proteins undergo significant rearrangement, these oocytes are unable to induce similar changes in transcriptionally active nuclei even after a prolonged culture interval.
- MeSH
- buněčné jádro enzymologie genetika MeSH
- cytoplazma enzymologie MeSH
- histondeacetylasa 1 metabolismus MeSH
- myši inbrední ICR MeSH
- myši MeSH
- oocyty enzymologie ultrastruktura MeSH
- přeprogramování buněk fyziologie MeSH
- RNA-polymerasa II metabolismus MeSH
- techniky jaderného přenosu MeSH
- umlčování genů * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Hdac1 protein, mouse MeSH Prohlížeč
- histondeacetylasa 1 MeSH
- RNA-polymerasa II MeSH