Sex chromosome silencing in the marsupial male germ line. Proc Natl Acad Sci USA

Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 07/2007; 104(23):9730-5. DOI: 10.1073/pnas.0700323104
Source: PubMed


In marsupials, dosage compensation involves silencing of the father's X-chromosome. Because no XIST orthologue has been found, how imprinted X-inactivation occurs is unknown. In eutherians, the X is subject to meiotic sex chromosome inactivation (MSCI) in the paternal germ line and persists thereafter as postmeiotic sex chromatin (PMSC). One hypothesis proposes that the paternal X is inherited by the eutherian zygote as a preinactive X and raises the possibility of a similar process in the marsupial germ line. Here we demonstrate that MSCI and PMSC occur in the opossum. Surprisingly, silencing occurs before X-Y association. After MSCI, the X and Y fuse through a dense plate without obvious synapsis. Significantly, sex chromosome silencing continues after meiosis, with the opossum PMSC sharing features of eutherian PMSC. These results reveal a common gametogenic program in two diverse clades of mammals and support the idea that male germ-line silencing may have provided an ancestral form of mammalian dosage compensation.

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Available from: Satoshi Namekawa, May 08, 2014
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    • "Recent advances in the biology of sex chromosomes , summarized above , enable us to revisit old evolutionary theories of sex chromosomes . In this section , we discuss the driving forces and strategies that have shaped the evolution of the sex chromosomes . MSCI is common between eutherians and marsupials ( Hornecker et al . 2007 , Namekawa et al . 2007 ) , and is considered to have evolved with the emergence of the XY chromosomes in therian ancestors ( Potrzebowski et al . 2008 ) . With this history , gene reactivation within the context of sex chromosome inactivation was a necessary step to acquire the spermiogenesis functions of the sex chromosomes ."
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    ABSTRACT: Mammalian sex chromosomes arose from an ordinary pair of autosomes. Over hundreds of millions of years, they have evolved into highly divergent X and Y chromosomes and have become increasingly specialized for male reproduction. Both sex chromosomes have acquired and amplified testis-specific genes, suggestive of roles in spermatogenesis. To understand how the sex chromosome genes participate in the regulation of spermatogenesis, we review genes, including single-copy, multi-copy, and ampliconic genes, whose spermatogenic functions have been demonstrated in mouse genetic studies. Sex chromosomes are subject to chromosome-wide transcriptional silencing in meiotic and postmeiotic stages of spermatogenesis. We also discuss particular sex-linked genes that escape postmeiotic silencing and their evolutionary implications. The unique gene contents and genomic structures of the sex chromosomes reflect their strategies to express genes at various stages of spermatogenesis and reveal the driving forces that shape their evolution.
    Reproduction (Cambridge, England) 05/2015; 149(6):R265-R277. DOI:10.1530/REP-14-0613 · 3.17 Impact Factor
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    • "The first form, meiotic sex chromosome inactivation (MSCI), occurs during spermatogenesis in eutherians and marsupials at the pachytene stage when all homologous chromosomes are paired with synaptonemal complexes. Heteromorphic X- and Y-chromosomes become transcriptionally inactive and form so-called sex or XY-body [1], [2], [3], [4]. The transcriptional suppression initiated by MSCI does not end with meiosis I, but is sustained in meiosis II and is manifested as postmeiotic sex chromatin (PMSC) during spermiogenesis [5]. "
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    ABSTRACT: In rodent female mammals, there are two forms of X-inactivation - imprinted and random which take place in extraembryonic and embryonic tissues, respectively. The inactive X-chromosome during random X-inactivation was shown to contain two types of facultative heterochromatin that alternate and do not overlap. However, chromatin structure of the inactive X-chromosome during imprinted X-inactivation, especially at early stages, is still not well understood. In this work, we studied chromatin modifications associated with the inactive X-chromosome at different stages of imprinted X-inactivation in a rodent, Microtus levis. It has been found that imprinted X-inactivation in vole occurs in a species-specific manner in two steps. The inactive X-chromosome at early stages of imprinted X-inactivation is characterized by accumulation of H3K9me3, HP1, H4K20me3, and uH2A, resembling to some extent the pattern of repressive chromatin modifications of meiotic sex chromatin. Later, the inactive X-chromosome recruits trimethylated H3K27 and acquires the two types of heterochromatin associated with random X-inactivation.
    PLoS ONE 02/2014; 9(2):e88256. DOI:10.1371/journal.pone.0088256 · 3.23 Impact Factor
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    • "Next, to determine whether epigenetic silencing of the sex chromosomes is maintained after meiosis in human round spermatids, we sought to identify human PMSC. Previously, we showed that heterochromatin proteins CBX1 (also known as HP1b) and CBX3 (also known as HP1g) and trimethylation of histone H3 lysine 9 (H3K9me3) were conserved markers of PMSC both in mice and opossums (Namekawa et al. 2007). In humans, we found that CBX1, CBX3, and H3K9me3 start to accumulate on the sex chromosomes in the pachytene-to-diplotene transition during meiosis (Fig. 1D; Supplemental Fig. S1; Metzler-Guillemain et al. 2003). "
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    ABSTRACT: Sex chromosome inactivation is essential epigenetic programming in male germ cells. However, it remains largely unclear how epigenetic silencing of sex chromosomes impacts the evolution of the mammalian genome. Here we demonstrate that male sex chromosome inactivation is highly conserved between humans and mice and has an impact on the genetic evolution of human sex chromosomes. We show that, in humans, sex chromosome inactivation established during meiosis is maintained into spermatids with the silent compartment postmeiotic sex chromatin (PMSC). Human PMSC is illuminated with epigenetic modifications such as trimethylated lysine 9 of histone H3 and heterochromatin proteins CBX1 and CBX3, which implicate a conserved mechanism underlying the maintenance of sex chromosome inactivation in mammals. Furthermore, our analyses suggest that male sex chromosome inactivation has impacted multiple aspects of the evolutionary history of mammalian sex chromosomes: amplification of copy number, retrotranspositions, acquisition of de novo genes, and acquisition of different expression profiles. Most strikingly, profiles of escape genes from postmeiotic silencing diverge significantly between humans and mice. Escape genes exhibit higher rates of amino acid changes compared with non-escape genes, suggesting that they are beneficial for reproductive fitness and may allow mammals to cope with conserved postmeiotic silencing during the evolutionary past. Taken together, we propose that the epigenetic silencing mechanism impacts the genetic evolution of sex chromosomes and contributed to speciation and reproductive diversity in mammals.
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