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Biology of Reproduction Apr 2024Histone post-translational modifications, such as phosphorylation, methylation, acetylation, and ubiquitination, play vital roles in various chromatin-based cellular... (Review)
Review
Histone post-translational modifications, such as phosphorylation, methylation, acetylation, and ubiquitination, play vital roles in various chromatin-based cellular processes. Meiosis is crucial for organisms that depend on sexual reproduction to produce haploid gametes, during which chromatin undergoes intricate conformational changes. An increasing body of evidence is clarifying the essential roles of histone post-translational modifications during meiotic divisions. In this review, we concentrate on the post-translational modifications of H2A, H2B, H3, and H4, as well as the linker histone H1, that are required for meiosis, and summarize recent progress in understanding how these modifications influence diverse meiotic events. Finally, challenges and exciting open questions for future research in this field are discussed. Summary Sentence Diverse histone post-translational modifications exert important effects on the meiotic cell cycle and these "histone codes" in meiosis might lead to the development of novel therapeutic strategies against reproductive diseases.
Topics: Histones; Chromatin; Protein Processing, Post-Translational; Phosphorylation; Meiosis; Acetylation
PubMed: 38224305
DOI: 10.1093/biolre/ioae011 -
Journal of Advanced Research Sep 2023The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer...
INTRODUCTION
The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics.
OBJECTIVES
Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process.
METHODS
In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry.
RESULTS
R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage.
CONCLUSION
The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis.
Topics: Male; Mice; Animals; R-Loop Structures; DNA Breaks, Double-Stranded; Meiosis; Spermatogenesis; Spermatocytes; Mice, Knockout; Mammals
PubMed: 36396044
DOI: 10.1016/j.jare.2022.10.016 -
The Plant Journal : For Cell and... Jun 2024Efficient chromatin condensation is required to transport chromosomes during mitosis and meiosis, forming daughter cells. While it is well accepted that these processes... (Review)
Review
Efficient chromatin condensation is required to transport chromosomes during mitosis and meiosis, forming daughter cells. While it is well accepted that these processes follow fundamental rules, there has been a controversial debate for more than 140 years on whether the higher-order chromatin organization in chromosomes is evolutionarily conserved. Here, we summarize historical and recent investigations based on classical and modern methods. In particular, classical light microscopy observations based on living, fixed, and treated chromosomes covering a wide range of plant and animal species, and even in single-cell eukaryotes suggest that the chromatids of large chromosomes are formed by a coiled chromatin thread, named the chromonema. More recently, these findings were confirmed by electron and super-resolution microscopy, oligo-FISH, molecular interaction data, and polymer simulation. Altogether, we describe common and divergent features of coiled chromonemata in different species. We hypothesize that chromonema coiling in large chromosomes is a fundamental feature established early during the evolution of eukaryotes to handle increasing genome sizes.
Topics: Chromatin; Eukaryota; Chromatids; Meiosis; Mitosis; Animals; Chromosomes, Plant; Plants
PubMed: 37840457
DOI: 10.1111/tpj.16484 -
Frontiers in Endocrinology 2023Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis... (Review)
Review
Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis typically does not directly harm the oocyte, but rather inhibits the function of granulosa cells, resulting in a decrease in oocyte quality. Granulosa cells, as oocyte nanny cells, can regulate meiosis, provide the most basic resources required for oocyte development, and influence ovulation. Endometriosis affects oocyte development and quality by causing granulosa cells apoptosis, inflammation, oxidative stress, steroid synthesis obstacle, and aberrant mitochondrial energy metabolism. These aberrant states frequently interact with one another, however there is currently relatively little research in this field to understand the mechanism of linkage between abnormal states.
Topics: Female; Humans; Endometriosis; Oocytes; Granulosa Cells; Apoptosis; Meiosis
PubMed: 37664845
DOI: 10.3389/fendo.2023.1226687 -
Andrology Mar 2024Telomeres are unique structures situated at the ends of chromosomes. Preserving the structure and function of telomeres is essential for maintaining genomic stability... (Review)
Review
BACKGROUND
Telomeres are unique structures situated at the ends of chromosomes. Preserving the structure and function of telomeres is essential for maintaining genomic stability and promoting genetic diversity during male meiosis in mammals.
MATERIAL-METHODS
This review compiled recent literature on the function and regulation of telomeres during male meiosis in both mice and humans, and also highlighted the critical roles of telomeres in reproductive biology and medicine.
RESULTS-DISCUSSION
Various structures, consisting of the LINC complex (SUN-KASH), SPDYA-CDK2, TTM trimer (TERB1-TERB2-MAJIN), and shelterin, are critical in controlling telomeric activities, such as nuclear envelope attachment and bouquet formation. Other than telomere-related proteins, cohesins and genes responsible for regulating telomere function are also highlighted, though the exact mechanism remains unclear. The gene-mutant mouse models with meiotic defects directly reveal the essential roles of telomeres in male meiosis. Recently reported mutant genes associated with telomere activity in clinical practice have also been illustrated in detail.
CONCLUSIONS
Proper regulation of telomere activities is essential for male meiosis progression in mice and humans.
PubMed: 38511802
DOI: 10.1111/andr.13631 -
Nature Communications Nov 2023Embryo development depends upon maternally derived materials. Mammalian oocytes undergo extreme asymmetric cytokinesis events, producing one large egg and two small...
Embryo development depends upon maternally derived materials. Mammalian oocytes undergo extreme asymmetric cytokinesis events, producing one large egg and two small polar bodies. During cytokinesis in somatic cells, the midbody and subsequent assembly of the midbody remnant, a signaling organelle containing RNAs, transcription factors and translation machinery, is thought to influence cellular function or fate. The role of the midbody and midbody remnant in gametes, in particular, oocytes, remains unclear. Here, we examined the formation and function of meiotic midbodies (mMB) and mMB remnants using mouse oocytes and demonstrate that mMBs have a specialized cap structure that is orientated toward polar bodies. We show that that mMBs are translationally active, and that mMB caps are required to retain nascent proteins in eggs. We propose that this specialized mMB cap maintains genetic factors in eggs allowing for full developmental competency.
Topics: Animals; Mice; Meiosis; Oocytes; Cytokinesis; Polar Bodies; Embryonic Development; Mammals
PubMed: 37973997
DOI: 10.1038/s41467-023-43288-x -
Nature Communications Oct 2023The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly...
The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly regulated. FIGNL1 AAA+++ ATPase controls RAD51-mediated recombination in human cells. However, its role in gametogenesis remains unsolved. Here, we characterized a germ line-specific conditional knockout (cKO) mouse of FIGNL1. Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on meiotic chromosomes, supporting a positive role of FIGNL1 in homologous recombination at a post-assembly stage of RAD51/DMC1 filaments. Fignl1 cKO spermatocytes also accumulate RAD51/DMC1 on chromosomes in pre-meiotic S-phase. These RAD51/DMC1 assemblies are independent of meiotic DSB formation. We also showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. These results suggest an additional role of FIGNL1 in limiting the non-productive assembly of RAD51/DMC1 on native dsDNAs during pre-meiotic S-phase and meiotic prophase I.
Topics: Male; Humans; Animals; Mice; Meiosis; Rad51 Recombinase; DNA-Binding Proteins; ATPases Associated with Diverse Cellular Activities; DNA Breaks, Double-Stranded; Cell Cycle Proteins; Homologous Recombination; DNA; DNA Replication; Microtubule-Associated Proteins; Nuclear Proteins
PubMed: 37891173
DOI: 10.1038/s41467-023-42576-w -
Advanced Science (Weinheim,... Jan 2024ADP-ribosylation factor 1 (Arf1) is a small GTPase belonging to the Arf family. As a molecular switch, Arf1 is found to regulate retrograde and intra-Golgi transport,...
ADP-ribosylation factor 1 (Arf1) is a small GTPase belonging to the Arf family. As a molecular switch, Arf1 is found to regulate retrograde and intra-Golgi transport, plasma membrane signaling, and organelle function during mitosis. This study aimed to explore the noncanonical roles of Arf1 in cell cycle regulation and cytoskeleton dynamics in meiosis with a mouse oocyte model. Arf1 accumulated in microtubules during oocyte meiosis, and the depletion of Arf1 led to the failure of polar body extrusion. Unlike mitosis, it finds that Arf1 affected Myt1 activity for cyclin B1/CDK1-based G2/M transition, which disturbed oocyte meiotic resumption. Besides, Arf1 modulated GM130 for the dynamic changes in the Golgi apparatus and Rab35-based vesicle transport during meiosis. Moreover, Arf1 is associated with Ran GTPase for TPX2 expression, further regulating the Aurora A-polo-like kinase 1 pathway for meiotic spindle assembly and microtubule stability in oocytes. Further, exogenous Arf1 mRNA supplementation can significantly rescue these defects. In conclusion, results reported the noncanonical functions of Arf1 in G2/M transition and meiotic spindle organization in mouse oocytes.
Topics: Mice; Animals; ADP-Ribosylation Factor 1; Spindle Apparatus; GTP Phosphohydrolases; Meiosis; Oocytes; Golgi Apparatus
PubMed: 38014604
DOI: 10.1002/advs.202303009 -
Nucleic Acids Research Sep 2023Recruitment of RAD51 and/or DMC1 recombinases to single-strand DNA is indispensable for homology search and strand invasion in homologous recombination (HR) and for...
Recruitment of RAD51 and/or DMC1 recombinases to single-strand DNA is indispensable for homology search and strand invasion in homologous recombination (HR) and for protection of nascent DNA strands at stalled replication forks. Thereafter RAD51/DMC1 dissociate, actively or passively, from these joint molecules upon DNA repair or releasing from replication stress. However, the mechanism that regulates RAD51/DMC1 dissociation and its physiological importance remain elusive. Here, we show that a FLIP-FIGNL1 complex regulates RAD51 and DMC1 dissociation to promote meiotic recombination and replication fork restart in mammals. Mice lacking FLIP are embryonic lethal, while germline-specific deletion of FLIP leads to infertility in both males and females. FLIP-null meiocytes are arrested at a zygotene-like stage with massive RAD51 and DMC1 foci, which frequently co-localize with SHOC1 and TEX11. Furthermore, FLIP interacts with FIGNL1. Depletion of FLIP or FIGNL1 in cell lines destabilizes each other and impairs RAD51 dissociation. Thus, the active dissociation of RAD51/DMC1 by the FLIP-FIGNL1 complex is a crucial step required for HR and replication fork restart, and represents a conserved mechanism in somatic cells and germ cells.
Topics: Male; Female; Animals; Mice; DNA-Binding Proteins; Rad51 Recombinase; Homologous Recombination; DNA Replication; DNA; Cell Cycle Proteins; Meiosis; Mammals
PubMed: 37439366
DOI: 10.1093/nar/gkad596 -
Current Opinion in Genetics &... Aug 2023The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the... (Review)
Review
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
Topics: Animals; Female; Centromere; Meiosis; Germ Cells; Alleles; Mammals
PubMed: 37406428
DOI: 10.1016/j.gde.2023.102082