scholarly journals The X and Y Chromosomes Assemble into H2A.Z, Containing Facultative Heterochromatin, following Meiosis

2006 ◽  
Vol 26 (14) ◽  
pp. 5394-5405 ◽  
Author(s):  
Ian K. Greaves ◽  
Danny Rangasamy ◽  
Michael Devoy ◽  
Jennifer A. Marshall Graves ◽  
David J. Tremethick
Keyword(s):  
Large Scale ◽  
Sex Chromosome ◽  
Round Spermatid ◽  
Sequential Process ◽  
Facultative Heterochromatin ◽  
Unique Role ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Spermatogonia Stem Cells ◽  
Key Steps

ABSTRACT Spermatogenesis is a complex sequential process that converts mitotically dividing spermatogonia stem cells into differentiated haploid spermatozoa. Not surprisingly, this process involves dramatic nuclear and chromatin restructuring events, but the nature of these changes are poorly understood. Here, we linked the appearance and nuclear localization of the essential histone variant H2A.Z with key steps during mouse spermatogenesis. H2A.Z cannot be detected during the early stages of spermatogenesis, when the bulk of X-linked genes are transcribed, but its expression begins to increase at pachytene, when meiotic sex chromosome inactivation (MSCI) occurs, peaking at the round spermatid stage. Strikingly, when H2A.Z is present, there is a dynamic nuclear relocalization of heterochromatic marks (HP1β and H3 di- and tri-methyl K9), which become concentrated at chromocenters and the inactive XY body, implying that H2A.Z may substitute for the function of these marks in euchromatin. We also show that the X and the Y chromosome are assembled into facultative heterochromatic structures postmeiotically that are enriched with H2A.Z, thereby replacing macroH2A. This indicates that XY silencing continues following MSCI. These results provide new insights into the large-scale changes in the composition and organization of chromatin associated with spermatogenesis and argue that H2A.Z has a unique role in maintaining sex chromosomes in a repressed state.

scholarly journals Deficiency of SYCP3-related XLR3 Disrupts the Initiation of Meiotic Sex Chromosome Inactivation in Mouse Spermatogenesis

2021 ◽  
Author(s):  
Michael John O'Neill ◽  
Natali Sobel Naveh ◽  
Robert Foley ◽  
Katelyn DeNegre ◽  
Tristan Evans ◽  
...  
Keyword(s):  
Sex Chromosomes ◽  
Transcriptional Repression ◽  
Sex Chromosome ◽  
Chromosome Inactivation ◽  
Nuclear Compartment ◽  
Xy Body ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Multiple Clusters ◽  
Sex Chromosome Inactivation

In mammals, the X and Y chromosomes share only small regions of homology called pseudo-autosomal regions (PAR) where pairing and recombination in spermatocytes can occur. Consequently, the sex chromosomes remain largely unsynapsed during meiosis I and are sequestered in a nuclear compartment known as the XY body where they are transcriptionally silenced in a process called meiotic sex chromosome inactivation (MSCI). MSCI mirrors meiotic silencing of unpaired chromatin (MSUC), the sequestration and transcriptional repression of unpaired DNA observed widely in eukaryotes. MSCI is initiated by the assembly of the axial elements of the synaptonemal complex (SC) comprising the structural proteins SYCP2 and SYCP3 followed by the ordered recruitment of DNA Damage Response (DDR) factors to effect gene silencing. However, the precise mechanism of how unsynapsed chromatin is detected in meiocytes is poorly understood. The sex chromosomes in eutherian mammals harbor multiple clusters of SYCP3-like amplicons comprising the Xlr gene family, only a handful of which have been functionally studied. We used a shRNA-transgenic mouse model to create a deficiency in the testis-expressed multicopy Xlr3 genes to investigate their role in spermatogenesis. Here we show that knockdown of Xlr3 in mice leads to spermatogenic defects and a skewed sex ratio that can be traced to MSCI breakdown. Spermatocytes deficient in XLR3 form the XY body and the SC axial elements therein, but are compromised in their ability to recruit DDR components to the XY body.

scholarly journals Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility†

2017 ◽  
Vol 97 (2) ◽  
pp. 313-323 ◽  
Author(s):  
Lauren Wichman ◽  
Saigopal Somasundaram ◽  
Christine Breindel ◽  
Dana M. Valerio ◽  
John R. McCarrey ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Noncoding Rna ◽  
Sex Chromosome ◽  
Sperm Count ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Small Noncoding Rnas ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Dynamic Expression

Abstract Mammalian reproduction requires that males and females produce functional haploid germ cells through complex cellular differentiation processes known as spermatogenesis and oogenesis, respectively. While numerous studies have functionally characterized protein-coding genes and small noncoding RNAs (microRNAs and piRNAs) that are essential for gametogenesis, the roles of regulatory long noncoding RNAs (lncRNAs) are yet to be fully characterized. Previously, we and others have demonstrated that intergenic regions of the mammalian genome encode thousands of long noncoding RNAs, and many studies have now demonstrated their critical roles in key biological processes. Thus, we postulated that some lncRNAs may also impact mammalian spermatogenesis and fertility. In this study, we identified a dynamic expression pattern of lncRNAs during murine spermatogenesis. Importantly, we identified a subset of lncRNAs and very few mRNAs that appear to escape meiotic sex chromosome inactivation, an epigenetic process that leads to the silencing of the X- and Y-chromosomes at the pachytene stage of meiosis. Further, some of these lncRNAs and mRNAs show a strong testis expression pattern suggesting that they may play key roles in spermatogenesis. Lastly, we generated a mouse knockout of one X-linked lncRNA, Tslrn1 (testis-specific long noncoding RNA 1), and found that males carrying a Tslrn1 deletion displayed normal fertility but a significant reduction in spermatozoa. Our findings demonstrate that dysregulation of specific mammalian lncRNAs is a novel mechanism of low sperm count or infertility, thus potentially providing new biomarkers and therapeutic strategies.

scholarly journals Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation

2008 ◽  
Vol 182 (2) ◽  
pp. 263-276 ◽  
Author(s):  
Shantha K. Mahadevaiah ◽  
Déborah Bourc'his ◽  
Dirk G. de Rooij ◽  
Timothy H. Bestor ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Male Meiosis ◽  
Chromosome Inactivation ◽  
Null Mouse ◽  
Dna Double Strand Breaks ◽  
Meiotic Silencing ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Meiotic Dsbs ◽  
Sex Chromosome Inactivation

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.

The XY Body of the Cat (Felis catus): Structural Differentiations and Protein Immunolocalization

2017 ◽  
Vol 152 (3) ◽  
pp. 137-147 ◽  
Author(s):  
Roberta B. Sciurano ◽  
Geraldine De Luca ◽  
I. Mónica Rahn ◽  
Alberto J. Solari
Keyword(s):  
Sex Chromosome ◽  
Structural Characteristics ◽  
Domestic Cat ◽  
Xy Body ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Extreme Degree ◽  
Special Location ◽  
Pairing Region

The heteromorphic X and Y chromosomes behave in a special way in mammalian spermatocytes; they form the XY body and synapse only partially. The aim of this article was to study the origin and the role of the special differentiations in the XY pair of the domestic cat during pachytene by analyzing its fine structural characteristics and the immunolocalization of the main meiotic proteins SYCP3, SYCP1, SYCE3, SMC3, γ-H2AX, BRCA1, H3K27me3, and MLH1. The cat XY body shows particularly striking structures: an extreme degree of axial fibrillation in late pachynema and a special location of SYCP3-containing fibrils, bridging different regions of the main X axis, as well as one bridge at the inner end of the pairing region that colocalizes with the single mandatory MLH1 focus. There are sequential changes, first bullous expansions, then subdivision into fibrils, all involving axial thickening. The chromatin of the XY body presents the usual features of meiotic sex chromosome inactivation. An analysis of the XY body of many eutherians and metatherians suggests that axial thickenings are primitive features. The sequential changes in the mass and location of SYCP3-containing fibers vary among the clades because of specific processes of axial assembly/disassembly occurring in different species.

scholarly journals Epigenetic Dysregulation of Mammalian Male Meiosis Caused by Interference of Recombination and Synapsis

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2311
Author(s):  
Roberto de la Fuente ◽  
Florencia Pratto ◽  
Abrahan Hernández-Hernández ◽  
Marcia Manterola ◽  
Pablo López-Jiménez ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Male Meiosis ◽  
Epigenetic Marks ◽  
Prophase I ◽  
Recombination Proteins ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Genes Encoding

Meiosis involves a series of specific chromosome events, namely homologous synapsis, recombination, and segregation. Disruption of either recombination or synapsis in mammals results in the interruption of meiosis progression during the first meiotic prophase. This is usually accompanied by a defective transcriptional inactivation of the X and Y chromosomes, which triggers a meiosis breakdown in many mutant models. However, epigenetic changes and transcriptional regulation are also expected to affect autosomes. In this work, we studied the dynamics of epigenetic markers related to chromatin silencing, transcriptional regulation, and meiotic sex chromosome inactivation throughout meiosis in knockout mice for genes encoding for recombination proteins SPO11, DMC1, HOP2 and MLH1, and the synaptonemal complex proteins SYCP1 and SYCP3. These models are defective in recombination and/or synapsis and promote apoptosis at different stages of progression. Our results indicate that impairment of recombination and synapsis alter the dynamics and localization pattern of epigenetic marks, as well as the transcriptional regulation of both autosomes and sex chromosomes throughout prophase-I progression. We also observed that the morphological progression of spermatocytes throughout meiosis and the dynamics of epigenetic marks are processes that can be desynchronized upon synapsis or recombination alteration. Moreover, we detected an overlap of early and late epigenetic signatures in most mutants, indicating that the normal epigenetic transitions are disrupted. This can alter the transcriptional shift that occurs in spermatocytes in mid prophase-I and suggest that the epigenetic regulation of sex chromosomes, but also of autosomes, is an important factor in the impairment of meiosis progression in mammals.

105. MEIOTIC ACROBATS: MONOTREME SEX CHROMOSOME ORGANISATION DURING SPERMATOGENESIS

2010 ◽  
Vol 22 (9) ◽  
pp. 23
Author(s):  
F. Grutzner ◽  
A. Casey ◽  
T. Daish
Keyword(s):  
Sex Chromosomes ◽  
Meiotic Prophase ◽  
Sex Chromosome ◽  
National Academy Of Sciences ◽  
Prophase I ◽  
Meiotic Prophase I ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Specific Order ◽  
Active Transcription

Monotremes feature an extraordinarily complex sex chromosome system which shares extensive homology with bird sex chromosomes but no homology to sex chromosomes of other mammals (1,2,3). At meiotic prophase I the ten sex chromosomes in platypus (nine in echidna) assemble in a sex chromosome chain. We previously identified the multiple sex chromosomes in platypus and echidna that form the meiotic chain in males (1,2,4). We showed that sex chromosomes assembly in the chain in a specific order (5) and that they segregate alternately (1). In secondary spermatocytes we observed clustering of X and Y chromosomes in sperm (6). Our current research investigates the formation of the synaptonemal complex, recombination and meiotic silencing of monotreme sex chromosomes. Meiotic sex chromosome inactivation (MSCI) has been observed in eutherian mammals, marsupials and birds but has so far not been investigated experimentally in monotremes. We found that during pachytene the X5Y5 end of the chain closely associates with the nucleolus and accumulates repressive chromatin marks (e.g. histone variant mH2A). In contrast to the differential accumulation of mH2A we observe extensive loading of the cohesin SMC3 on sex chromosomes in particular during the pachytene stage of meiotic prophase I. We have also used markers of active transcription and gene expression analysis to investigate gene activity in platypus meiotic cells. I will discuss how these findings contribute to our current understanding of the meiotic organisation of monotreme sex chromosomes and the evolution of MSCI in birds and mammals. (1) Grützner et al. (2004), Nature 432: 913–917.(2) Rens et al. (2007), Genome Biology 16;8(11): R243.(3) Veyrunes et al. (2008), Genome Research, 18(6): 995–1004.(4) Rens et al. (2004), Proceedings of the National Academy of Sciences USA. 101 (46): 16 257–16 261.(5) Daish et al. (2009), Reprod Fertil Dev. 21(8): 976–84.(6) Tsend-Ayush et al. (2009), Chromosoma 118(1): 53–69.

M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis

2001 ◽  
Vol 114 (18) ◽  
pp. 3367-3375 ◽  
Author(s):  
James M. A. Turner ◽  
Paul S. Burgoyne ◽  
Prim B. Singh
Keyword(s):  
Meiotic Prophase ◽  
Sex Chromosome ◽  
Centromeric Heterochromatin ◽  
Pseudoautosomal Region ◽  
Male And Female ◽  
Female Mice ◽  
Steroid Sulphatase ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Surface Spread

Progression through meiotic prophase is associated with dramatic changes in chromosome condensation. Two proteins that have been implicated in effecting these changes are the mammalian HP1-like protein M31 (HP1β or MOD1) and the unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes. This second observation has raised the possibility that these proteins co-operate in meiotic sex chromosome inactivation. In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice. Using this approach, we report that, in addition to their previous described staining patterns, both proteins localise to a focus within the portion of the pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In light of the timing of its appearance and of its behaviour in sex-chromosomally variant mice, we suggest a role for this heterochromatin focus in preventing complete desynapsis of the terminally associated X and Y chromosomes prior to anaphase I.

scholarly journals The male germline-specific protein MAPS is indispensable for pachynema progression and fertility

2021 ◽  
Vol 118 (8) ◽  
pp. e2025421118
Author(s):  
Miao Li ◽  
Jiahuan Zheng ◽  
Gaopeng Li ◽  
Zexiong Lin ◽  
Dongliang Li ◽  
...  
Keyword(s):  
Large Scale ◽  
Sex Chromosome ◽  
Strand Break ◽  
Specific Protein ◽  
Pachytene Stage ◽  
Protein Ubiquitination ◽  
Male Germline ◽  
Meiotic Sex Chromosome Inactivation ◽  
Pachytene Spermatocytes

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 1700102P08Rik, 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 Maps (Maps−/−) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps−/− 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 Maps−/− 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 Maps−/− 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 Maps−/− 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.

scholarly journals Telomere-to-telomere assembly of a fish Y chromosome reveals the origin of a young sex chromosome pair

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lingzhan Xue ◽  
Yu Gao ◽  
Meiying Wu ◽  
Tian Tian ◽  
Haiping Fan ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Sex Chromosomes ◽  
Chromosome Pair ◽  
Sex Chromosome ◽  
Structural Variations ◽  
Recombination Suppression ◽  
Chromosome Differentiation ◽  
Y Chromosomes ◽  
Recent Origin ◽  
Mastacembelus Armatus

Abstract Background The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, providing species for studying how and why recombination suppression evolved in the initial stages of sex chromosome differentiation, but this requires accurate sequence assembly of the X and Y (or Z and W) chromosomes, which may be difficult if they are recently diverged. Results Here we produce a haplotype-resolved genome assembly of zig-zag eel (Mastacembelus armatus), an aquaculture fish, at the chromosomal scale. The diploid assembly is nearly gap-free, and in most chromosomes, we resolve the centromeric and subtelomeric heterochromatic sequences. In particular, the Y chromosome, including its highly repetitive short arm, has zero gaps. Using resequencing data, we identify a ~7 Mb fully sex-linked region (SLR), spanning the sex chromosome centromere and almost entirely embedded in the pericentromeric heterochromatin. The SLRs on the X and Y chromosomes are almost identical in sequence and gene content, but both are repetitive and heterochromatic, consistent with zero or low recombination. We further identify an HMG-domain containing gene HMGN6 in the SLR as a candidate sex-determining gene that is expressed at the onset of testis development. Conclusions Our study supports the idea that preexisting regions of low recombination, such as pericentromeric regions, can give rise to SLR in the absence of structural variations between the proto-sex chromosomes.

scholarly journals Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes

2001 ◽  
Vol 78 (1) ◽  
pp. 23-30 ◽  
Author(s):  
MARIKO KONDO ◽  
ERIKO NAGAO ◽  
HIROSHI MITANI ◽  
AKIHIRO SHIMA
Keyword(s):  
Genetic Map ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Oryzias Latipes ◽  
Male Recombination ◽  
Male And Female ◽  
Y Chromosomes ◽  
Genetic Length ◽  
Expressed Sequence ◽  
Group 1

In the medaka, Oryzias latipes, sex is determined chromosomally. The sex chromosomes differ from those of mammals in that the X and Y chromosomes are highly homologous. Using backcross panels for linkage analysis, we mapped 21 sequence tagged site (STS) markers on the sex chromosomes (linkage group 1). The genetic map of the sex chromosome was established using male and female meioses. The genetic length of the sex chromosome was shorter in male than in female meioses. The region where male recombination is suppressed is the region close to the sex-determining gene y, while female recombination was suppressed in both the telomeric regions. The restriction in recombination does not occur uniformly on the sex chromosome, as the genetic map distances of the markers are not proportional in male and female recombination. Thus, this observation seems to support the hypothesis that the heterogeneous sex chromosomes were derived from suppression of recombination between autosomal chromosomes. In two of the markers, Yc-2 and Casp6, which were expressed sequence-tagged (EST) sites, polymorphisms of both X and Y chromosomes were detected. The alleles of the X and Y chromosomes were also detected in O. curvinotus, a species related to the medaka. These markers could be used for genotyping the sex chromosomes in the medaka and other species, and could be used in other studies on sex chromosomes.

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