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In mammalian male gametogenesis the sex chromosomes are distinctive in both gene activity and epigenetic strategy. At first meiotic prophase the heteromorphic X and Y chromosomes are placed in a separate chromatin domain called the XY body. In this process, X,Y chromatin becomes highly phosphorylated at S139 of H2AX leading to the repression of gonosomal genes, a process known as meiotic sex chromosome inactivation (MSCI), which has been studied best in mice. Post-meiotically this repression is largely maintained. Disturbance of MSCI in mice leads to harmful X,Y gene expression, eventuating in spermatocyte death and sperm heterogeneity. Sperm heterogeneity is a characteristic of the human male. For this reason we were interested in the efficiency of MSCI in human primary spermatocytes. We investigated MSCI in pachytene spermatocytes of seven probands: four infertile men and three fertile controls, using direct and indirect in situ methods. A considerable degree of variation in the degree of MSCI was detected, both between and within probands. Moreover, in post-meiotic stages this variation was observed as well, indicating survival of spermatocytes with incompletely inactivated sex chromosomes. Furthermore, we investigated the presence of H3K9me3 posttranslational modifications on the X and Y chromatin. Contrary to constitutive centromeric heterochromatin, this heterochromatin marker did not specifically accumulate on the XY body, with the exception of the heterochromatic part of the Y chromosome. This may reflect the lower degree of MSCI in man compared to mouse. These results point at relaxation of MSCI, which can be explained by genetic changes in sex chromosome composition during evolution and candidates as a mechanism behind human sperm heterogeneity. 相似文献
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Mahadevaiah SK Bourc'his D de Rooij DG Bestor TH Turner JM Burgoyne PS 《The Journal of cell biology》2008,182(2):263-276
Chromosome synapsis during zygotene is a prerequisite for the timely homologous recombinational repair of meiotic DNA double-strand breaks (DSBs). Unrepaired DSBs are thought to trigger apoptosis during midpachytene of male meiosis if synapsis fails. An early pachytene response to asynapsis is meiotic silencing of unsynapsed chromatin (MSUC), which, in normal males, silences the X and Y chromosomes (meiotic sex chromosome inactivation [MSCI]). In this study, we show that MSUC occurs in Spo11-null mouse spermatocytes with extensive asynapsis but lacking meiotic DSBs. In contrast, three mutants (Dnmt3l, Msh5, and Dmc1) with high levels of asynapsis and numerous persistent unrepaired DSBs have a severely impaired MSUC response. We suggest that MSUC-related proteins, including the MSUC initiator BRCA1, are sequestered at unrepaired DSBs. All four mutants fail to silence the X and Y chromosomes (MSCI failure), which is sufficient to explain the midpachytene apoptosis. Apoptosis does not occur in mice with a single additional asynapsed chromosome with unrepaired meiotic DSBs and no disturbance of MSCI. 相似文献
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Royo H Polikiewicz G Mahadevaiah SK Prosser H Mitchell M Bradley A de Rooij DG Burgoyne PS Turner JM 《Current biology : CB》2010,20(23):2117-2123
The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-), and Msh5(-/-). However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of individual Y genes inserted as transgenes on autosomes shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis. 相似文献
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As a group, sex chromosome aneuploidies - the 47,XXY, 47,XYY, 47,XXX and 45,X conditions - constitute the most common class of chromosome abnormality in human live-births. Considerable attention has been given to the somatic abnormalities associated with these conditions, but less is known about their meiotic phenotypes; that is, how does sex chromosome imbalance influence the meiotic process. This has become more important with the advent of assisted reproductive technologies, because individuals previously thought to be infertile can now become biological parents. Indeed, there are several recent reports of successful pregnancies involving 47,XXY fathers, and suggestions that cryopreservation of ovarian tissue might impart fertility to at least some Turner syndrome individuals. Thus, the possible consequences of sex chromosome aneuploidy on meiotic chromosome segregation need to be explored. 相似文献
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Scherthan H 《Cytogenetic and genome research》2003,103(3-4):235-244
Meiosis is a succession of two specialized cell divisions that leads to the formation of gametes and thereby compensates for genome doubling at fertilization. During the extended prophase of the first meiotic division chromosomes assemble protein cores (axial elements) that attach their ends to the nuclear envelope. These ends transiently gather at a limited sector of the nuclear periphery (bouquet stage) at a time when meiotic recombination is initiated and when chromosomes initiate stable pairing (synapsis). This review discusses novel insights into the relation between recombinational DNA repair and meiotic telomere dynamics that have arrived from recent studies of transchromosomal mice and knockout mice. Analysis of mice deficient for A-type lamins, histone H2AX, Suv39h HMTases, and the AE protein SYCP3 suggests that entry into prophase I requires heterochromatin integrity and lamin A expression. Initiation of meiotic telomere clustering represents an early recombination-independent event in first meiotic prophase, while exit from the bouquet stage depends on signals that emanate from the progress of recombinational DNA repair as sensed by ATM kinase and relayed through histone H2AX. 相似文献
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Forsburg SL 《Molecular cell》2002,9(4):703-711
The process of meiosis reduces a diploid cell to four haploid gametes and is accompanied by extensive recombination. Thus, chromosome dynamics in meiosis are significantly different than in mitotic cells. This review analyzes unique features of meiotic DNA replication and describes how it affects subsequent recombination and chromosome segregation. 相似文献
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A characteristic feature of spider karyotypes is the predominance of unusual multiple X chromosomes. To elucidate the evolution of spider sex chromosomes, their meiotic behavior was analyzed in 2 major clades of opisthothele spiders, namely, the entelegyne araneomorphs and the mygalomorphs. Our data support the predominance of X(1)X(2)0 systems in entelegynes, while rare X(1)X(2)X(3)X(4)0 systems were revealed in the tuberculote mygalomorphs. The spider species studied exhibited a considerable diversity of achiasmate sex chromosome pairing in male meiosis. The end-to-end pairing of sex chromosomes found in mygalomorphs was gradually replaced by the parallel attachment of sex chromosomes in entelegynes. The observed association of male X univalents with a centrosome at the first meiotic division may ensure the univalents' segregation. Spider meiotic sex chromosomes also showed other unique traits, namely, association with a chromosome pair in males and inactivation in females. Analysis of these traits supports the hypothesis that the multiple X chromosomes of spiders originated by duplications. In contrast to the homogametic sex of other animals, the homologous sex chromosomes of spider females were already paired at premeiotic interphase and were inactivated until prophase I. Furthermore, the sex chromosome pairs exhibited an end-to-end association during these stages. We suggest that the specific behavior of the female sex chromosomes may have evolved to avoid the negative effects of duplicated X chromosomes on female meiosis. The chromosome ends that ensure the association of sex chromosome pairs during meiosis may contain information for discriminating between homologous and homeologous X chromosomes and thus act to promote homologous pairing. The meiotic behavior of 4 X chromosome pairs in mygalomorph females, namely, the formation of 2 associations, each composed of 2 pairs with similar structure, suggests that the mygalomorph X(1)X(2)X(3)X(4)0 system originated by the duplication of the X(1)X(2)0 system via nondisjunctions or polyploidization. 相似文献
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Chromosome shaping and individualization are necessary requisites to warrant the correct segregation of genomes in either mitotic or meiotic cell divisions. These processes are mainly prompted in vertebrates by three multiprotein complexes termed cohesin and condensin I and II. In the present study we have analyzed by immunostaining the appearance and subcellular distribution of condensin I in mouse mitotic and meiotic chromosomes. Our results demonstrate that in either mitotically or meiotically dividing cells, condensin I is loaded onto chromosomes by prometaphase. Condensin I is detectable as a fuzzy axial structure running inside chromatids of condensed chromosomes. The distribution of condensin I along the chromosome length is not uniform, since it preferentially accumulates close to the chromosome ends. Interestingly, these round accumulations found at the condensin I axes termini colocalized with telomere complexes. Additionally, we present the relative distribution of the condensin I and cohesin complexes in metaphase I bivalents. All these new data have allowed us to propose a comprehensive model for meiotic chromosome structure. 相似文献
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The existing XYY meiotic data for mice present a very heterogeneous picture with respect to the relative frequencies of different sex chromosome associations, both at pachytene and diakinesis/metaphase I. Furthermore, where both pachytene and diakinesis/MI data are available for the same males, the frequencies of the different configurations at the two stages are very different. In the present paper we utilise "XYY" and "XY/XYY" mosaic mice with cytologically distinguishable Y chromosomes to investigate the factors responsible for this heterogeneity between different males and between the two meiotic stages. It is concluded (1) that the initial pattern of synapsis is driven by the relatedness of the three pseudoautosomal regions (PARs); (2) that the order and extent of PAR synapsis within radial trivalents are also affected by PAR relatedness and that this leads to chiasmata being preferentially formed between closely related PARs; (3) that trivalents with a single chiasma resolve into a bivalent + univalent by the diakinesis stage; (4) that although many spermatocytes with asynapsed sex chromosomes are eliminated between pachytene and diakinesis, those that survive this phase of elimination progress to the first meiotic metaphase (MI) and accumulate in large numbers, leading to an over-representation of those with univalents as compared to radial trivalents; and (5) that the arrested MI cells are eventually eliminated, so that very few "XYY" cells contribute products to MII. 相似文献
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Heterogeneity for the length of telomeric DNA sequences has been found among different mitotic chromosomes in several mammalian species. However, there are no studies reporting such heterogeneity in meiotic chromosomes. To analyse this heterogeneity we have performed fluorescence in situ hybridization with a telomeric (C(3)TA(2))(3) peptide nucleic acid (PNA) probe on spread metaphase chromosomes during both male mouse meiotic divisions. Our results show that independently of the meiotic division, telomeric DNA signals were always surrounded by DAPI-stained chromatin, even at centromeric regions. Moreover, we have found heterogeneity for the size of telomeric DNA signals among different chromosomes, between homologues, and even within a given chromosome. We discuss the functional significance of the location of telomeric DNA in condensed meiotic chromosomes, and then the possible origin for the different polymorphisms found. 相似文献
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A Role for SUMO in meiotic chromosome synapsis 总被引:1,自引:0,他引:1
During meiotic prophase, homologous chromosomes engage in a complex series of interactions that ensure their proper segregation at meiosis I. A central player in these interactions is the synaptonemal complex (SC), a proteinaceous structure elaborated along the lengths of paired homologs. In mutants that fail to make SC, crossing over is decreased, and chromosomes frequently fail to recombine; consequently, many meiotic products are inviable because of aneuploidy. Here, we have investigated the role of the small ubiquitin-like protein modifier (SUMO) in SC formation during meiosis in budding yeast. We show that SUMO localizes specifically to synapsed regions of meiotic chromosomes and that this localization depends on Zip1, a major building block of the SC. A non-null allele of the UBC9 gene, which encodes the SUMO-conjugating enzyme, impairs Zip1 polymerization along chromosomes. The Ubc9 protein localizes to meiotic chromosomes, coincident with SUMO staining. In the zip1 mutant, SUMO localizes to discrete foci on chromosomes. These foci coincide with axial associations, where proteins involved in synapsis initiation are located. Our data suggest a model in which SUMO modification of chromosomal proteins promotes polymerization of Zip1 along chromosomes. The ubc9 mutant phenotype provides the first evidence for a cause-and-effect relationship between sumoylation and synapsis. 相似文献
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The effect of telomere heterochromatin on metaphase I association of chromosome pair 1R of rye was analyzed in normal diploid plants of rye (2n=14) and in wheat-rye derivatives with the chromosome constitution (0–7)A(0–7)BRR (2n=20, 21 and 22). The C-banding pattern of 1R was variable between plants. In diploid rye the presence or absence of telomeric heterochromatin in 1R does not influence its meiotic pairing. However, in wheat-rye derivatives the presence of telomeric heterochromatin decreases chiasma frequency in the 1R bivalent. This cannot be attributed to interference of heterochromatin with chiasma terminalization. This effect of heterochromatin is most pronounced in heterozygous condition. In plants heterozygous for telomeric C-bands the reduction of pairing is stronger in the short arm than in the long arm of the 1R bivalent. 相似文献
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Revenkova E Eijpe M Heyting C Hodges CA Hunt PA Liebe B Scherthan H Jessberger R 《Nature cell biology》2004,6(6):555-562
Sister chromatid cohesion ensures the faithful segregation of chromosomes in mitosis and in both meiotic divisions. Meiosis-specific components of the cohesin complex, including the recently described SMC1 isoform SMC1 beta, were suggested to be required for meiotic sister chromatid cohesion and DNA recombination. Here we show that SMC1 beta-deficient mice of both sexes are sterile. Male meiosis is blocked in pachytene; female meiosis is highly error-prone but continues until metaphase II. Prophase axial elements (AEs) are markedly shortened, chromatin extends further from the AEs, chromosome synapsis is incomplete, and sister chromatid cohesion in chromosome arms and at centromeres is lost prematurely. In addition, crossover-associated recombination foci are absent or reduced, and meiosis-specific perinuclear telomere arrangements are impaired. Thus, SMC1 beta has a key role in meiotic cohesion, the assembly of AEs, synapsis, recombination, and chromosome movements. 相似文献