Article

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: 9.81). 07/2007; 104(23):9730-5. DOI: 10.1073/pnas.0700323104
Source: PubMed

ABSTRACT 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 ."
    Reproduction (Cambridge, England) 05/2015; 149(6):R265-R277. DOI:10.1530/REP-14-0613 · 3.26 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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    • "However, genomic analyses of paternal XCI in the marsupial Monodelphis domestica (the South American opossum) and mice provide conflicting viewpoints on the evolutionary origins of paternal imprinting in mice. A study based on Cot-1 RNA fluorescence in situ analysis supports the claim that the imprinted paternal X is the basal condition in therian mammals; the paternal X chromosome in the opossum is inactivated during meiosis and this inactive state is maintained following spermatogenesis (Namekawa et al. 2007). However, research based on transcript profiling of X-linked genes suggests that paternal imprinting in mice may be a derived characteristic (Mahadevaiah et al. 2009). "
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    ABSTRACT: Our understanding of the evolution of sex chromosomes has increased greatly in recent years due to a number of molecular evolutionary investigations in divergent sex chromosome systems, and these findings are reshaping theories of sex chromosome evolution. In particular, the dynamics of the sex-determining region (SDR) have been demonstrated by recent findings in ancient and incipient sex chromosomes. Radical changes in genomic structure and gene content in the male specific region of the Y chromosome between human and chimpanzee indicated rapid evolution in the past 6 million years, defying the notion that the pace of evolution in the SDR was fast at early stages but slowed down overtime. The chicken Z and the human X chromosomes appeared to have acquired testis-expressed genes and expanded in intergenic regions. Transposable elements greatly contributed to SDR expansion and aided the trafficking of genes in the SDR and its X or Z counterpart through retrotransposition. Dosage compensation is not a destined consequence of sex chromosomes as once thought. Most X-linked microRNA genes escape silencing and are expressed in testis. Collectively, these findings are challenging many of our preconceived ideas of the evolutionary trajectory and fates of sex chromosomes.
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