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Developmental Cell Dec 2023During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the...
During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the chromatin remodeling in oogenesis and characteristics of homologous pairing remain largely elusive. We comprehensively compared chromatin structures and transcriptomes at successive substages of meiotic prophase in both female and male mice using low-input high-through chromosome conformation capture (Hi-C) and RNA sequencing (RNA-seq). Compartments and topologically associating domains (TADs) gradually disappeared and slowly recovered in both sexes. We found that homologs adopted different sex-conserved pairing strategies prior to and after the leptotene-to-zygotene transition, changing from long interspersed nuclear element (LINE)-enriched compartments B to short interspersed nuclear element (SINE)-enriched compartments A. We complemented marker genes and predicted the sex-specific meiotic sterile genes for each substage. This study provides valuable insights into the similarities and distinctions between sexes in chromosome architecture, homologous pairing, and transcriptome during meiotic prophase of both oogenesis and spermatogenesis.
Topics: Male; Female; Mice; Animals; Meiosis; Spermatogenesis; Prophase; Meiotic Prophase I; Chromatin; Oogenesis; Chromosome Pairing
PubMed: 37963468
DOI: 10.1016/j.devcel.2023.10.009 -
Frontiers in Cell and Developmental... 2021Germ cells undergoing meiosis rely on an intricate network of surveillance mechanisms that govern the production of euploid gametes for successful sexual reproduction.... (Review)
Review
Germ cells undergoing meiosis rely on an intricate network of surveillance mechanisms that govern the production of euploid gametes for successful sexual reproduction. These surveillance mechanisms are particularly crucial during meiotic prophase, when cells execute a highly orchestrated program of chromosome morphogenesis and recombination, which must be integrated with the meiotic cell division machinery to ensure the safe execution of meiosis. Dynamic protein phosphorylation, controlled by kinases and phosphatases, has emerged as one of the main signaling routes for providing readout and regulation of chromosomal and cellular behavior throughout meiotic prophase. In this review, we discuss common principles and provide detailed examples of how these phosphorylation events are employed to ensure faithful passage of chromosomes from one generation to the next.
PubMed: 33928091
DOI: 10.3389/fcell.2021.667073 -
Cells Jun 2023The synaptonemal complex (SC) is a meiosis-specific multiprotein complex that forms between homologous chromosomes during prophase of meiosis I. Upon assembly, the SC... (Review)
Review
The synaptonemal complex (SC) is a meiosis-specific multiprotein complex that forms between homologous chromosomes during prophase of meiosis I. Upon assembly, the SC mediates the synapses of the homologous chromosomes, leading to the formation of bivalents, and physically supports the formation of programmed double-strand breaks (DSBs) and their subsequent repair and maturation into crossovers (COs), which are essential for genome haploidization. Defects in the assembly of the SC or in the function of the associated meiotic recombination machinery can lead to meiotic arrest and human infertility. The majority of proteins and complexes involved in these processes are exclusively expressed during meiosis or harbor meiosis-specific subunits, although some have dual functions in somatic DNA repair and meiosis. Consistent with their functions, aberrant expression and malfunctioning of these genes have been associated with cancer development. In this review, we focus on the significance of the SC and their meiotic-associated proteins in human fertility, as well as how human genetic variants encoding for these proteins affect the meiotic process and contribute to infertility and cancer development.
Topics: Synaptonemal Complex; Humans; Meiosis; Neoplasms; Infertility; Male; Female; Recombination, Genetic
PubMed: 37443752
DOI: 10.3390/cells12131718 -
Annual Review of Plant Biology May 2022In contrast to well-studied fungal and animal cells, plant cells assemble bipolar spindles that exhibit a great deal of plasticity in the absence of structurally defined... (Review)
Review
In contrast to well-studied fungal and animal cells, plant cells assemble bipolar spindles that exhibit a great deal of plasticity in the absence of structurally defined microtubule-organizing centers like the centrosome. While plants employ some evolutionarily conserved proteins to regulate spindle morphogenesis and remodeling, many essential spindle assembly factors found in vertebrates are either missing or not required for producing the plant bipolar microtubule array. Plants also produce proteins distantly related to their fungal and animal counterparts to regulate critical events such as the spindle assembly checkpoint. Plant spindle assembly initiates with microtubule nucleation on the nuclear envelope followed by bipolarization into the prophase spindle. After nuclear envelope breakdown, kinetochore fibers are assembled and unified into the spindle apparatus with convergent poles. Of note, compared to fungal and animal systems, relatively little is known about how plant cells remodel the spindle microtubule array during anaphase. Uncovering mitotic functions of novel proteins for spindle assembly in plants will illuminate both common and divergent mechanisms employed by different eukaryotic organisms to segregate genetic materials.
Topics: Animals; Centrosome; Microtubules; Mitosis; Spindle Apparatus; Tubulin
PubMed: 35595291
DOI: 10.1146/annurev-arplant-070721-084258 -
Philosophical Transactions. Series A,... Jun 2021We report that high-density single-molecule super-resolution microscopy can be achieved with a conventional epifluorescence microscope set-up and a mercury arc lamp. The...
We report that high-density single-molecule super-resolution microscopy can be achieved with a conventional epifluorescence microscope set-up and a mercury arc lamp. The configuration termed as laser-free super-resolution microscopy (LFSM) is an extension of single-molecule localization microscopy (SMLM) techniques and allows single molecules to be switched on and off (a phenomenon termed as 'blinking'), detected and localized. The use of a short burst of deep blue excitation (350-380 nm) can be further used to reactivate the blinking, once the blinking process has slowed or stopped. A resolution of 90 nm is achieved on test specimens (mouse and amphibian meiotic chromosomes). Finally, we demonstrate that stimulated emission depletion and LFSM can be performed on the same biological sample using a simple commercial mounting medium. It is hoped that this type of correlative imaging will provide a basis for a further enhanced resolution. This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 1)'.
Topics: Amphibians; Animals; Chromosomes; Equipment Design; Fluorescent Dyes; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Organic Chemicals; Proof of Concept Study; Single Molecule Imaging; Synaptonemal Complex; Xanthenes
PubMed: 33896204
DOI: 10.1098/rsta.2020.0144 -
Sexual Development : Genetics,... 2022Meiosis is a crucial process for germ cell development. It consists of 1 round of DNA replication followed by 2 rounds of chromosome segregation, producing haploid... (Review)
Review
BACKGROUND
Meiosis is a crucial process for germ cell development. It consists of 1 round of DNA replication followed by 2 rounds of chromosome segregation, producing haploid gametes from diploid cells. During meiotic prophase, chromosomes are organized into axis-loop structures, which underlie meiosis-specific events such as meiotic recombination and homolog synapsis. Meiosis-specific cohesin plays a pivotal role in establishing higher-order chromosome architecture and regulating chromosome dynamics.
SUMMARY
Notably, sexually dimorphic properties of chromosome architecture are prominent during meiotic prophase, despite the same axial proteins being conserved between male and female. The difference in chromosome structure between the sexes gives sexual differences in the regulation of meiotic recombination and crossover distribution.
KEY MESSAGES
This review mainly focuses on the sexual differences of meiosis from the viewpoint of chromosome structure in mammals, elucidating the differences in meiotic recombination and homolog synapsis between the sexes.
PubMed: 35130542
DOI: 10.1159/000520682 -
Annual Review of Genetics Nov 2021The specialized two-stage meiotic cell division program halves a cell's chromosome complement in preparation for sexual reproduction. This reduction in ploidy requires... (Review)
Review
The specialized two-stage meiotic cell division program halves a cell's chromosome complement in preparation for sexual reproduction. This reduction in ploidy requires that in meiotic prophase, each pair of homologous chromosomes (homologs) identify one another and form physical links through DNA recombination. Here, we review recent advances in understanding the complex morphological changes that chromosomes undergo during meiotic prophase to promote homolog identification and crossing over. We focus on the structural maintenance of chromosomes (SMC) family cohesin complexes and the meiotic chromosome axis, which together organize chromosomes and promote recombination. We then discuss the architecture and dynamics of the conserved synaptonemal complex (SC), which assembles between homologs and mediates local and global feedback to ensure high fidelity in meiotic recombination. Finally, we discuss exciting new advances, including mechanisms for boosting recombination on particular chromosomes or chromosomal domains and the implications of a new liquid crystal model for SC assembly and structure.
Topics: Chromosome Pairing; Chromosomes; Homologous Recombination; Meiosis; Synaptonemal Complex
PubMed: 34530636
DOI: 10.1146/annurev-genet-071719-020235 -
Nucleus (Austin, Tex.) Dec 2024Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing... (Review)
Review
Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I.
Topics: Heterochromatin; Centromere; Meiosis; Chromosome Pairing
PubMed: 38488152
DOI: 10.1080/19491034.2024.2328719 -
Clinical and Translational Medicine Jul 2022An impeccable female meiotic prophase is critical for producing a high-quality oocyte and, ultimately, a healthy newborn. SYCP3 is a key component of the synaptonemal...
BACKGROUND
An impeccable female meiotic prophase is critical for producing a high-quality oocyte and, ultimately, a healthy newborn. SYCP3 is a key component of the synaptonemal complex regulating meiotic homologous recombination. However, what regulates SYCP3 stability is unknown.
METHODS
Fertility assays, follicle counting, meiotic prophase stage (leptotene, zygotene, pachytene and diplotene) analysis and live imaging were employed to examine how FBXW24 knockout (KO) affect female fertility, follicle reserve, oocyte quality, meiotic prophase progression of female germ cells, and meiosis of oocytes. Western blot and immunostaining were used to examined the levels & signals (intensity, foci) of SYCP3 and multiple key DSB indicators & repair proteins (γH2AX, RPA2, p-CHK2, RAD51, MLH1, HORMAD1, TRIP13) after FBXW24 KO. Co-IP and immuno-EM were used to examined the interaction between FBXW24 and SYCP3; Mass spec was used to characterize the ubiquitination sites in SYCP3; In vivo & in vitro ubiquitination assays were utilized to determine the key sites in SYCP3 & FBXW24 for ubiquitination.
RESULTS
Fbxw24-knockout (KO) female mice were infertile due to massive oocyte death upon meiosis entry. Fbxw24-KO oocytes were defective due to elevated DNA double-strand breaks (DSBs) and inseparable homologous chromosomes. Fbxw24-KO germ cells showed increased SYCP3 levels, delayed prophase progression, increased DSBs, and decreased crossover foci. Next, we found that FBXW24 directly binds and ubiquitinates SYCP3 to regulate its stability. In addition, several key residues important for SYCP3 ubiquitination and FBXW24 ubiquitinating activity were characterized.
CONCLUSIONS
We proposed that FBXW24 regulates the timely degradation of SYCP3 to ensure normal crossover and DSB repair during pachytene. FBXW24-KO delayed SYCP3 degradation and DSB repair from pachytene until metaphase II (MII), ultimately causing failure in oocyte maturation, oocyte death, and infertility.
Topics: Animals; Cell Cycle Proteins; DNA-Binding Proteins; F-Box Proteins; Female; Meiosis; Mice; Prophase; Synaptonemal Complex; Ubiquitination
PubMed: 35858239
DOI: 10.1002/ctm2.891 -
Current Opinion in Plant Biology Oct 2019Meiotic recombination provides genetic diversity in populations and ensures accurate homologous chromosome segregation for genome integrity. During meiosis,... (Review)
Review
Meiotic recombination provides genetic diversity in populations and ensures accurate homologous chromosome segregation for genome integrity. During meiosis, recombination processes, from DNA double strand breaks (DSBs) to crossover formation are tightly linked to higher order chromosome structure, including chromatid cohesion, axial element formation, homolog pairing and synapsis. The extensive studies on plant meiosis have revealed the important conserved roles for meiotic proteins in homologous recombination. Recent works have focused on elucidating the mechanistic basis of how meiotic proteins regulate recombination events via protein complex formation and modifications such as phosphorylation, ubiquitination, and SUMOylation. Here, we highlight recent advances on the signaling and modifications of meiotic proteins that mediate the formation of DSBs and crossovers in plants.
Topics: Chromosome Pairing; DNA Breaks, Double-Stranded; DNA Repair; Homologous Recombination; Meiosis
PubMed: 31048232
DOI: 10.1016/j.pbi.2019.04.001