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Yasushi Hiraoka - One of the best experts on this subject based on the ideXlab platform.
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A cohesin-based structural platform supporting homologous Chromosome Pairing in meiosis
Current Genetics, 2016Co-Authors: Daqiao Ding, Tokuko Haraguchi, Yasushi HiraokaAbstract:The Pairing and recombination of homologous Chromosomes during the meiotic prophase is necessary for the accurate segregation of Chromosomes in meiosis. However, the mechanism by which homologous Chromosomes achieve this Pairing has remained an open question. Meiotic cohesins have been shown to affect chromatin compaction; however, the impact of meiotic cohesins on homologous Pairing and the fine structures of cohesion-based chromatin remain to be determined. A recent report using live-cell imaging and super-resolution microscopy demonstrated that the lack of meiotic cohesins alters the Chromosome axis structures and impairs the Pairing of homologous Chromosomes. These results suggest that meiotic cohesin-based Chromosome axis structures are crucial for the Pairing of homologous Chromosomes.
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dynamics of homologous Chromosome Pairing during meiotic prophase in fission yeast
Developmental Cell, 2004Co-Authors: Daqiao Ding, Ayumu Yamamoto, Tokuko Haraguchi, Yasushi HiraokaAbstract:Pairing of homologous Chromosomes is important for homologous recombination and correct Chromosome segregation during meiosis. It has been proposed that telomere clustering, nuclear oscillation, and recombination during meiotic prophase facilitate homologous Chromosome Pairing in fission yeast. Here we examined the contributions of these chromosomal events to homologous Chromosome Pairing, by directly observing the dynamics of chromosomal loci in living cells of fission yeast. Homologous loci exhibited a dynamic process of association and dissociation during the time course of meiotic prophase. Lack of nuclear oscillation reduced association frequency for both centromeric and arm regions of the Chromosome. Lack of telomere clustering or recombination reduced association frequency at arm regions, but not significantly at centromeric regions. Our results indicate that homologous Chromosomes are spatially aligned by oscillation of telomere-bundled Chromosomes and physically linked by recombination at Chromosome arm regions; this recombination is not required for association of homologous centromeres.
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the onset of homologous Chromosome Pairing during drosophila melanogaster embryogenesis
Journal of Cell Biology, 1993Co-Authors: Yasushi Hiraoka, Abby F. Dernburg, Susan J Parmelee, Mary C Rykowski, David A Agard, John W. SedatAbstract:We have determined the position within the nucleus of homologous sites of the histone gene cluster in Drosophila melanogaster using in situ hybridization and high-resolution, three-dimensional wide field fluorescence microscopy. A 4.8-kb biotinylated probe for the histone gene repeat, located approximately midway along the short arm of Chromosome 2, was hybridized to whole-mount embryos in late syncytial and early cellular blastoderm stages. Our results show that the two homologous histone loci are distinct and separate through all stages of the cell cycle up to nuclear cycle 13. By dramatic contrast, the two homologous clusters were found to colocalize with high frequency during interphase of cycle 14. Concomitant with homolog Pairing at cycle 14, both histone loci were also found to move from their position near the midline of the nucleus toward the apical side. This result suggests that coincident with the initiation of zygotic transcription, there is dramatic Chromosome and nuclear reorganization between nuclear cycles 13 and 14.
Jeannie T Lee - One of the best experts on this subject based on the ideXlab platform.
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par terra directs homologous sex Chromosome Pairing
Nature Structural & Molecular Biology, 2017Co-Authors: Jeannie T Lee, Stefan F Pinter, Hsuehping Chu, John E Froberg, Barry Kesner, Ruslan I SadreyevAbstract:In mammals, homologous Chromosomes rarely pair outside meiosis. One exception is the X Chromosome, which transiently pairs during X-Chromosome inactivation (XCI). How two Chromosomes find each other in 3D space is not known. Here, we reveal a required interaction between the X-inactivation center (Xic) and the telomere in mouse embryonic stem (ES) cells. The subtelomeric, pseudoautosomal regions (PARs) of the two sex Chromosomes (X and Y) also undergo Pairing in both female and male cells. PARs transcribe a class of telomeric RNA, dubbed PAR-TERRA, which accounts for a vast majority of all TERRA transcripts. PAR-TERRA binds throughout the genome, including to the PAR and Xic. During X-Chromosome Pairing, PAR-TERRA anchors the Xic to the PAR, creating a 'tetrad' of pairwise homologous interactions (Xic-Xic, PAR-PAR, and Xic-PAR). Xic Pairing occurs within the tetrad. Depleting PAR-TERRA abrogates Pairing and blocks initiation of XCI, whereas autosomal PAR-TERRA induces ectopic Pairing. We propose a 'constrained diffusion model' in which PAR-TERRA creates an interaction hub to guide Xic homology searching during XCI.
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characterization of xpr xpct reveals instability but no effects on x Chromosome Pairing or xist expression
Transcription, 2010Co-Authors: Sha Sun, Ruslan I Sadreyev, Yoshiro Fukue, Leisha Nolen, Jeannie T LeeAbstract:X-Chromosome inactivation balances X-Chromosome dosages in male and female mammals by transcriptionally repressing one X in the female sex. Proper counting and the mutually exclusive choice of active X and inactive X have been hypothesized to involve X-Chromosome crosstalk via homologous Chromosome Pairing. Transient Pairing of two female Xs requires noncoding Tsix and Xite. A recent study suggested a new Pairing element (Xpr), located ~200 kb upstream of Xist, in the Xpct region. Xpr is proposed to induce Pairing and activate Xist expression. Here, we further characterize Xpr and find that the Xpr sequence is unstable when introduced as transgenes into male ES cells. Xpr transgenes show an unusual tendency to disperse throughout the nucleus. However, we observe neither Pairing between Xpr alleles nor ectopic Xist expression. In the absence of Tsix, Xpr does not induce inter-allelic Xic interactions. Female ES cells carrying Xpr transgenes are more stable. Nonetheless, Pairing also does not seem to occur ...
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the pluripotency factor oct4 interacts with ctcf and also controls x Chromosome Pairing and counting
Nature, 2009Co-Authors: Mary E Donohoe, Susana S Silva, Stefan F Pinter, Jeannie T LeeAbstract:Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-Chromosome inactivation (XCI) in which one female X Chromosome is silenced to achieve gene dosage parity between the sexes. Somatic XCI is regulated by homologous X-Chromosome Pairing and counting, and by the random choice of future active and inactive X Chromosomes. XCI and cell differentiation are tightly coupled, as blocking one process compromises the other and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X Chromosome reactivation. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-Chromosome Pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-Chromosome Pairing and results in the inactivation of both X Chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-Chromosome reprogramming.
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evidence that homologous x Chromosome Pairing requires transcription and ctcf protein
Nature Genetics, 2007Co-Authors: Mary E Donohoe, Susana S Silva, Jeannie T LeeAbstract:X-Chromosome inactivation (XCI) ensures the equality of X-Chromosome dosages in male and female mammals by silencing one X in the female1. To achieve the mutually exclusive designation of active X (Xa) and inactive X (Xi), the process necessitates that two Xs communicate in trans through homologous Pairing2,3. Pairing depends on a 15-kb region within the genes Tsix and Xite2. Here, we dissect molecular requirements and find that Pairing can be recapitulated by 1- to 2-kb subfragments of Tsix or Xite with little sequence similarity. However, a common denominator among them is the presence of the protein Ctcf, a chromatin insulator4,5,6,7 that we find to be essential for Pairing. By contrast, the Ctcf-interacting partner, Yy1 (ref. 8), is not required. Pairing also depends on transcription. Transcriptional inhibition prevents new pair formation but does not perturb existing pairs. The kinetics suggest a Pairing half-life of <1 h. We propose that Pairing requires Ctcf binding and co-transcriptional activity of Tsix and Xite.
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transient homologous Chromosome Pairing marks the onset of x inactivation
Science, 2006Co-Authors: Chialun Tsai, Jeannie T LeeAbstract:Mammalian X inactivation turns off one female X Chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal Pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs Pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome Pairing. Ectopic X-autosome interactions inhibit endogenous X-X Pairing and block the initiation of X-Chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X Pairing.
Shirleen G Roeder - One of the best experts on this subject based on the ideXlab platform.
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the mnd1 protein forms a complex with hop2 to promote homologous Chromosome Pairing and meiotic double strand break repair
Molecular and Cellular Biology, 2002Co-Authors: Hideo Tsubouchi, Shirleen G RoederAbstract:The hop2 mutant of Saccharomyces cerevisiae arrests in meiosis with extensive synaptonemal complex (SC) formation between nonhomologous Chromosomes. A screen for multicopy suppressors of a hop2-ts allele identified the MND1 gene. The mnd1-null mutant arrests in meiotic prophase, with most double-strand breaks (DSBs) unrepaired. A low level of mature recombinants is produced, and the Rad51 protein accumulates at numerous foci along Chromosomes. SC formation is incomplete, and homolog Pairing is severely reduced. The Mnd1 protein localizes to chromatin throughout meiotic prophase, and this localization requires Hop2. Unlike recombination enzymes such as Rad51, Mnd1 localizes to Chromosomes even in mutants that fail to initiate meiotic recombination. The Hop2 and Mnd1 proteins coimmunoprecipitate from meiotic cell extracts. These results suggest that Hop2 and Mnd1 work as a complex to promote meiotic Chromosome Pairing and DSB repair. The identification of Hop2 and Mnd1 homologs in other organisms suggests that the function of this complex is conserved among eukaryotes.
P M Borodin - One of the best experts on this subject based on the ideXlab platform.
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cytological basis of sterility in male and female hybrids between sibling species of grey voles microtus arvalis and m levis
Scientific Reports, 2016Co-Authors: Anna A Torgasheva, P M BorodinAbstract:To make insight into the cytological basis of reproductive isolation, we examined Chromosome synapsis and recombination in sterile male and female hybrids between Microtus arvalis and M. levis. These sibling species differ by a series of chromosomal rearrangements (fusions, inversions, centromere shifts and heterochromatin insertions). We found that meiosis in male hybrids was arrested at leptotene with complete failure of Chromosome Pairing and DNA double-strand breaks repair. In the female hybrids meiosis proceeded to pachytene; however, the oocytes varied in the degree of Pairing errors. Some of them demonstrated almost correct Chromosome Pairing, while most of them contained a varying number of univalents and multivalents with extensive regions of asynapsis and non-homologous synapsis. Variation between oocytes was probably caused by stochasticity in the ratio of homologous to non-homologous Pairing initiations. We suggest that substantial chromosomal and genetic divergence between the parental species affects preliminary alignment of homologues, homology search and elimination of ectopic interhomologue interactions that are required for correct homologous Pairing. Apparently, Pairing failure in male and aberrant synapsis in female vole hybrids followed by meiotic silencing of unsynapsed chromatin cause apoptosis of gametocytes and sterility.
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a and b Chromosome Pairing and recombination in male meiosis of the silver fox vulpes vulpes l 1758 carnivora canidae
Chromosome Research, 2010Co-Authors: E A Basheva, Anna A Torgasheva, P M Borodin, Galia R Sakaeva, Claudio J BidauAbstract:We examined A- and B-Chromosome Pairing and recombination in 12 males from the farm-bred population of the silver fox (2n = 34 + 0-10 Bs) by means of electron and immunofluorescent microscopy. To detect recombination at A and B Chromosomes, we used immunolocalisation of MLH1, a mismatch repair protein of mature recombination nodules, at synaptonemal complexes. The mean total number of MLH1 foci at A-autosomes was 29.6 foci per cell. The XY bivalent had one MLH1 focus at the Pairing region. Total recombination length of the male fox genome map was estimated as 1,530 centimorgans. We detected single MLH1 foci at 61% of linear synaptic configurations involving B Chromosomes. The distribution of the foci along B- and A-bivalents was the same. This may be considered as a first molecular evidence that meiotic recombination does occur in mammalian B Chromosomes. There was no correlation between the number of synaptic configurations involving B Chromosomes per cell and the recombination rate of the A-genome.
John W. Sedat - One of the best experts on this subject based on the ideXlab platform.
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homologous Chromosome Pairing in drosophila melanogaster proceeds through multiple independent initiations
Journal of Cell Biology, 1998Co-Authors: Jennifer C Fung, Abby F. Dernburg, David A Agard, Wallace F Marshall, John W. SedatAbstract:The dynamics by which homologous Chromosomes pair is currently unknown. Here, we use fluorescence in situ hybridization in combination with three-dimensional optical microscopy to show that homologous Pairing of the somatic Chromosome arm 2L in Drosophila occurs by independent initiation of Pairing at discrete loci rather than by a processive zippering of sites along the length of Chromosome. By evaluating the Pairing frequencies of 11 loci on Chromosome arm 2L over several timepoints during Drosophila embryonic development, we show that all 11 loci are paired very early in Drosophila development, within 13 h after egg deposition. To elucidate whether such Pairing occurs by directed or undirected motion, we analyzed the Pairing kinetics of histone loci during nuclear cycle 14. By measuring changes of nuclear length and correlating these changes with progression of time during cycle 14, we were able to express the Pairing frequency and distance between homologous loci as a function of time. Comparing the experimentally determined dynamics of Pairing to simulations based on previously proposed models of Pairing motion, we show that the observed Pairing kinetics are most consistent with a constrained random walk model and not consistent with a directed motion model. Thus, we conclude that simple random contacts through diffusion could suffice to allow Pairing of homologous sites.
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the onset of homologous Chromosome Pairing during drosophila melanogaster embryogenesis
Journal of Cell Biology, 1993Co-Authors: Yasushi Hiraoka, Abby F. Dernburg, Susan J Parmelee, Mary C Rykowski, David A Agard, John W. SedatAbstract:We have determined the position within the nucleus of homologous sites of the histone gene cluster in Drosophila melanogaster using in situ hybridization and high-resolution, three-dimensional wide field fluorescence microscopy. A 4.8-kb biotinylated probe for the histone gene repeat, located approximately midway along the short arm of Chromosome 2, was hybridized to whole-mount embryos in late syncytial and early cellular blastoderm stages. Our results show that the two homologous histone loci are distinct and separate through all stages of the cell cycle up to nuclear cycle 13. By dramatic contrast, the two homologous clusters were found to colocalize with high frequency during interphase of cycle 14. Concomitant with homolog Pairing at cycle 14, both histone loci were also found to move from their position near the midline of the nucleus toward the apical side. This result suggests that coincident with the initiation of zygotic transcription, there is dramatic Chromosome and nuclear reorganization between nuclear cycles 13 and 14.