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Genes Nov 2021Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes,...
Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes, transcription levels change during prophase-I, being low at the onset of meiosis but highly increased from pachytene up to the end of diplotene. However, X and Y chromosomes, which usually present unsynapsed regions throughout prophase-I in male meiosis, undergo a specific pattern of transcriptional inactivation. The interdependence of synapsis and transcription has mainly been studied in mammals, basically in mouse, but our knowledge in other unrelated phylogenetically species is more limited. To gain new insights on this issue, here we analyzed the relationship between synapsis and transcription in spermatocytes of the grasshopper . Autosomal chromosomes of this species achieve complete synapsis; however, the single X sex chromosome remains always unsynapsed and behaves as a univalent. We studied transcription in meiosis by immunolabeling with RNA polymerase II phosphorylated at serine 2 and found that whereas autosomes are active from leptotene up to diakinesis, the X chromosome is inactive throughout meiosis. This inactivation is accompanied by the accumulation of, at least, two repressive epigenetic modifications: H3 methylated at lysine 9 and H2AX phosphorylated at serine 139. Furthermore, we identified that X chromosome inactivation occurs in premeiotic spermatogonia. Overall, our results indicate: (i) transcription regulation in spermatogenesis differs from the canonical pattern found in mammals and (ii) X chromosome inactivation is likely preceded by a process of heterochromatinization before the initiation of meiosis.
Topics: Animals; Chromosome Pairing; Epigenesis, Genetic; Female; Gene Silencing; Grasshoppers; Histones; Lysine; Male; Meiosis; Meiotic Prophase I; RNA Polymerase II; Spermatocytes; Spermatogenesis; X Chromosome; X Chromosome Inactivation; Y Chromosome
PubMed: 34946793
DOI: 10.3390/genes12121844 -
Frontiers in Cell and Developmental... 2022How eukaryotic cells control their duplication is a fascinating example of how a biological system self-organizes specific activities to temporally order cellular... (Review)
Review
How eukaryotic cells control their duplication is a fascinating example of how a biological system self-organizes specific activities to temporally order cellular events. During cell cycle progression, the cellular level of CDK (Cyclin-Dependent Kinase) activity temporally orders the different cell cycle phases, ensuring that DNA replication occurs prior to segregation into two daughter cells. CDK activity requires the binding of a regulatory subunit (cyclin) to the core kinase, and both CDKs and cyclins are well conserved throughout evolution from yeast to humans. As key regulators, they coordinate cell cycle progression with metabolism, DNA damage, and cell differentiation. In meiosis, the special cell division that ensures the transmission of genetic information from one generation to the next, cyclins and CDKs have acquired novel functions to coordinate meiosis-specific events such as chromosome architecture, recombination, and synapsis. Interestingly, meiosis-specific cyclins and CDKs are common in evolution, some cyclins seem to have evolved to acquire CDK-independent functions, and even some CDKs associate with a non-cyclin partner. We will review the functions of these key regulators in meiosis where variation has specially flourished.
PubMed: 36523509
DOI: 10.3389/fcell.2022.1069064 -
Asian Journal of Andrology 2021The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various... (Review)
Review
The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.
Topics: Animals; Chromosome Segregation; Meiosis; Synaptonemal Complex
PubMed: 34528517
DOI: 10.4103/aja202153 -
Cell Cycle (Georgetown, Tex.) 2022Mammalian oocytes undergo two rounds of developmental arrest during maturation: at the diplotene of the first meiotic prophase and metaphase of the second meiosis. These... (Review)
Review
Mammalian oocytes undergo two rounds of developmental arrest during maturation: at the diplotene of the first meiotic prophase and metaphase of the second meiosis. These arrests are strictly regulated by follicular cells temporally producing the secondary messengers, cAMP and cGMP, and other factors to regulate maturation promoting factor (composed of cyclin B1 and cyclin-dependent kinase 1) levels in the oocytes. Out of these normally appearing developmental arrests, permanent arrests may occur in the oocytes at germinal vesicle (GV), metaphase I (MI), or metaphase II (MII) stage. This issue may arise from absence or altered expression of the oocyte-related genes playing key roles in nuclear and cytoplasmic maturation. Additionally, the assisted reproductive technology (ART) applications such as ovarian stimulation and culture conditions both of which harbor various types of chemical agents may contribute to forming the permanent arrests. In this review, the molecular determinants of developmental and permanent arrests occurring in the mammalian oocytes are comprehensively evaluated in the light of current knowledge. As number of permanently arrested oocytes at different stages is increasing in ART centers, potential approaches for inducing permanent arrests to obtain competent oocytes are discussed.
Topics: Animals; Mammals; Meiosis; Meiotic Prophase I; Metaphase; Oocytes
PubMed: 35072590
DOI: 10.1080/15384101.2022.2026704 -
ELife Oct 2023In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most...
In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most meiotic proteins are conserved between eggs and sperm, many aspects of meiosis are sexually dimorphic, including the regulation of recombination. The synaptonemal complex (SC), a large ladder-like structure that forms between homologous chromosomes, is essential for regulating meiotic chromosome organization and promoting recombination. To assess whether sex-specific differences in the SC underpin sexually dimorphic aspects of meiosis, we examined SC central region proteins (known as SYP proteins) in oogenesis and spermatogenesis and uncovered sex-specific roles for the SYPs in regulating meiotic recombination. We find that SC composition, specifically SYP-2, SYP-3, SYP-5, and SYP-6, is regulated by sex-specific mechanisms throughout meiotic prophase I. During pachytene, both oocytes and spermatocytes differentially regulate the stability of SYP-2 and SYP-3 within an assembled SC. Further, we uncover that the relative amount of SYP-2 and SYP-3 within the SC is independently regulated in both a sex-specific and a recombination-dependent manner. Specifically, we find that SYP-2 regulates the early steps of recombination in both sexes, while SYP-3 controls the timing and positioning of crossover recombination events across the genomic landscape in only oocytes. Finally, we find that SYP-2 and SYP-3 dosage can influence the composition of the other SYPs in the SC via sex-specific mechanisms during pachytene. Taken together, we demonstrate dosage-dependent regulation of individual SC components with sex-specific functions in recombination. These sexual dimorphic features of the SC provide insights into how spermatogenesis and oogenesis adapted similar chromosome structures to differentially regulate and execute recombination.
Topics: Animals; Female; Male; Caenorhabditis elegans; Synaptonemal Complex; Meiosis; Semen; Caenorhabditis elegans Proteins
PubMed: 37796106
DOI: 10.7554/eLife.84538 -
ELife Feb 2022The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair,...
The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.
Topics: Animals; Ataxia Telangiectasia Mutated Proteins; DNA Damage; DNA Repair; Male; Meiosis; Mice, Inbred C57BL; Morpholines; Phosphorylation; Proteome; Pyrimidines; RNA, Messenger; Signal Transduction; Spermatocytes; Testis; Mice
PubMed: 35133275
DOI: 10.7554/eLife.68648 -
Proceedings of the National Academy of... Feb 2021Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a...
Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking ( ) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.
Topics: Animals; Chromosome Pairing; DNA Repair; Female; Infertility, Male; Male; Meiosis; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins; Pachytene Stage; Sex Chromosomes; Spermatocytes; Spermatogenesis
PubMed: 33602822
DOI: 10.1073/pnas.2025421118 -
Frontiers in Cell and Developmental... 2023Actin is a multi-functional protein that is involved in numerous cellular processes including cytoskeleton regulation, cell migration, and cellular integrity. In these... (Review)
Review
Actin is a multi-functional protein that is involved in numerous cellular processes including cytoskeleton regulation, cell migration, and cellular integrity. In these processes, actin's role in respect to its structure, complex mechanical, and protein-binding properties has been studied primarily in the cytoplasmic and cellular membrane compartments. However, its role in somatic cell nuclei has recently become evident where it participates in transcription, chromatin remodeling, and DNA damage repair. What remains enigmatic is the involvement of nuclear actin in physiological processes that lead to the generation of germ cells, in general, and primary spermatocytes, in particular. Here, we will discuss the possible role and nuclear localization of actin during meiotic prophase I and its interaction with chromatin remodeling complexes, the latter being essential for the control of pairing of homologous chromosomes, cross-over formation, and recombination. It is our hope that this perspective article will extend the scope of actin's nuclear function in germ cells undergoing meiotic division.
PubMed: 38078006
DOI: 10.3389/fcell.2023.1295452 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2020Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis... (Review)
Review
Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis prophase I) is the most prominent feature of meiosis. During meiosis prophase I, synaptonemal complex (SC) formed between homologous chromosomes to promote the initiation and repair of programmed DNA double-strand breaks (DSBs), which is necessary for the correct recognition, pairing, recombination and separation of homologous chromosomes. In this paper, we reviewed the recent research progress on the composition and function of SC, discussed how the assembly of SC affected the repair of DSBs, and also summarized the known mutations on SC genes which were responsible for human reproductive disorders. On this basis, we also explored the future research direction of this field.
Topics: DNA Breaks, Double-Stranded; DNA Repair; Humans; Meiotic Prophase I; Synaptonemal Complex
PubMed: 32099986
DOI: No ID Found -
Current Topics in Developmental Biology 2023Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure... (Review)
Review
Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the conserved and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers.
Topics: Animals; Synaptonemal Complex; Meiosis; Chromosome Pairing; Chromatin; Neoplasms; Mammals
PubMed: 36681479
DOI: 10.1016/bs.ctdb.2022.04.008