Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials

Shevchenko, Alexander I.; Захарова, И. С.; Elisaphenko, Eugeny A.; Kolesnikov, Nicolay N.; Whitehead, Siobhan; Bird, Christine P.; Ross, Mark T.; Weidman, Jennifer R.; Jirtle, Randy L.; Karamysheva, T. V.; Rubtsov, N. B.; VandeBerg, John L.; Mazurok, Nina A.; Nesterova, Tatyana B.; Brockdorff, Neil; Zakian, Suren M.

doi:10.1007/s10577-006-1115-9

Cited by 58 publications

(43 citation statements)

References 22 publications

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“…Thus, spermatogenic events regulating transcriptional activity of the sex chromosomes are very well conserved in the marsupial and eutherian. This is in striking contrast to the absence of conservation in XIC elements that regulate XCI in the eutherian soma (39)(40)(41)(42). These data are consistent with a mechanism of im- printed XCI that would occur independent of XIST in the marsupial and make possible a mechanism that relies instead on inheritance of a silent X derived from the male germ line (5,25,(28)(29)(30).…”

Section: Resultsmentioning

confidence: 57%

“…Eutherian XCI is regulated by the X-inactivation center (XIC/Xic), which contains the noncoding genes Xist (32)(33)(34), Tsix (35)(36)(37), and Xite (38). Repeated attempts to find the XIC orthologue in marsupials have failed and instead find that the syntenic region is rearranged (39)(40)(41). Interestingly, a recent report suggests that the ancestral XIST was vertebrate LNX3, a protein-coding gene with functions still extant but unrelated to dosage compensation in the marsupial (42).…”

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confidence: 99%

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Sex chromosome silencing in the marsupial male germ line

Namekawa

VandeBerg

McCarrey

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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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.meiosis ͉ X-inactivation

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Section: Resultsmentioning

confidence: 57%

mentioning

confidence: 99%

Sex chromosome silencing in the marsupial male germ line

Namekawa

VandeBerg

McCarrey

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Although Xic clearly regulates imprinting in eutherians, XIC or an equivalent has yet to be identified in marsupials (11,12,22,55). The absence of a marsupial Xist suggests that an alternative means of silencing the X must occur in mammals.…”

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confidence: 99%

Two-Step Imprinted X Inactivation: Repeat versus Genic Silencing in the Mouse

Namekawa

Payer

Huynh

et al. 2010

Molecular and Cellular Biology

111

152

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Mammals compensate for unequal X-linked gene dosages between the sexes by inactivating one X chromosome in the female. In marsupials and in the early mouse embryo, X chromosome inactivation (XCI) is imprinted to occur selectively on the paternal X chromosome (X P ). The mechanisms and events underlying X P imprinting remain unclear. Here, we find that the imprinted X P can be functionally divided into two domains, one comprising traditional coding genes (genic) and the other comprising intergenic repetitive elements. X P repetitive element silencing occurs by the two-cell stage, does not require Xist, and occurs several divisions prior to genic silencing. In contrast, genic silencing initiates at the morula-toblastocyst stage and absolutely requires Xist. Genes translocate into the presilenced repeat region as they are inactivated, whereas active genes remain outside. Thus, during the gamete-embryo transition, imprinted XCI occurs in two steps, with repeat silencing preceding genic inactivation. Nucleolar association may underlie the epigenetic asymmetry of X P and X M . We hypothesize that transgenerational information (the imprint) is carried by repeats from the paternal germ line or that, alternatively, repetitive elements are silenced at the two-cell stage in a parent-of-origin-specific manner. Our model incorporates aspects of the so-called classical, de novo, and preinactivation hypotheses and suggests that Xist RNA functions relatively late during preimplantation mouse development.Genomic imprinting refers to a parent-of-origin effect on gene expression in the developing embryo (3, 57). The existence of imprinting in the mammal means that male and female gametes contribute significantly different information to the zygote. One important difference is illustrated by X chromosome inactivation (XCI), the mechanism of dosage compensation in the mammal that results in the silencing of one X chromosome in the female embryo (2,33,34,49,64). While the eutherian form of XCI occurs randomly in the soma, the marsupial form is imprinted to occur exclusively on the paternal X (X P ) (54). Imprinted XCI also occurs in some eutherians but is restricted to the preimplantation embryo and the extraembryonic tissues (25,37,47,60). Imprinted XCI precedes random XCI in the early mouse embryo and continues through the placental lineages. In the epiblast (embryo proper), transient X reactivation is followed by random XCI, which accounts for the mosaic pattern of inactivation seen in all somatic tissues of the eutherian.The mechanisms and developmental timing of imprinted XCI remain unclear and are much debated. In principle, the maternal or paternal germ line (or both) may differentially mark the X chromosomes, with the maternal imprint protecting the maternal X (X M ) from inactivation and/or the paternal mark predestining X P for inactivation. The search for parentspecific regulators frequently has focused on the X inactivation center (Xic) (7), an X-linked region harboring several noncoding regulators for random XCI. Xist pr...

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“…Physical mapping and bioinformatic analyses revealed that the region homologous to the X inactivation centre is disrupted by independent rearrangements in marsupials and monotremes (Hore et al 2007;Shevchenko et al 2007), and it was suggested that XIST evolved from a protein coding gene (Lnx3) in this region, whose loss of function coincided with pseudogenization of flanking genes (Duret et al 2006). These findings challenge a pivotal role in X inactivation for XIST and raise many fundamental questions about the mechanism and evolution of this important epigenetic system.…”

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confidence: 99%

Specific patterns of histone marks accompany X chromosome inactivation in a marsupial

et al. 2009

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The inactivation of one of the two X chromosomes in female placental mammals represents a remarkable example of epigenetic silencing. X inactivation occurs also in marsupial mammals, but is phenotypically different, being incomplete, tissuespecific and paternal. Paternal X inactivation occurs also in the extraembryonic cells of rodents, suggesting that imprinted X inactivation represents a simpler ancestral mechanism. This evolved into a complex and random process in placental mammals under the control of the XIST gene, involving notably variant and modified histones. Molecular mechanisms of X inactivation in marsupials are poorly known, but occur in the absence of an XIST homologue. We analysed the specific pattern of histone modifications using immunofluorescence on metaphasic chromosomes of a model kangaroo, the tammar wallaby. We found that all active marks are excluded from the inactive X in marsupials, as in placental mammals, so this represents a common feature of X inactivation throughout mammals. However, we were unable to demonstrate the accumulation of inactive histone marks, suggesting some fundamental differences in the molecular mechanism of X inactivation between marsupial and placental mammals. A better understanding of the epigenetic mechanisms underlying X inactivation in marsupials will provide important insights into the evolution of this complex process.

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Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials

Cited by 58 publications

References 22 publications

Sex chromosome silencing in the marsupial male germ line

Sex chromosome silencing in the marsupial male germ line

Two-Step Imprinted X Inactivation: Repeat versus Genic Silencing in the Mouse

Specific patterns of histone marks accompany X chromosome inactivation in a marsupial

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