Parental source of chromosome imprinting and its relevance for X chromosome inactivation

Lyon, Mary F.; Rastan, Sohaila

doi:10.1111/j.1432-0436.1984.tb01375.x

Cited by 85 publications

(33 citation statements)

References 33 publications

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“…The imprint could be of maternal or paternal origin, or both. The existence of a maternal resistance to XCI is supported by the fact that maternal disomy for the X chromosome results in early embryonic lethality due to deficient XCI (7,8). This maternal imprint, which would be laid down during oogenesis (9), may lie at the level of the Xist gene.…”

mentioning

confidence: 94%

Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

Patrat

Okamoto

Diabangouaya

et al. 2009

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

156

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In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene silencing have been the subject of debate. We performed a systematic, single-cell transcriptional analysis to examine the activity of the Xp chromosome for a panel of X-linked genes throughout early preimplantation development in the mouse. Rather than being preinactivated, we found the Xp to be fully active at the time of zygotic gene activation, with silencing beginning from the 4-cell stage onward. X-inactivation patterns were, however, surprisingly diverse between genes. Some loci showed early onset (4 -8-cell stage) of X inactivation, and some showed extremely late onset (postblastocyst stage), whereas others were never fully inactivated. Thus, we show that silencing of some X-chromosomal regions occurs outside of the usual time window and that escape from X inactivation can be highly lineage specific. These results reveal that imprinted X inactivation in mice is far less concerted than previously thought and highlight the epigenetic diversity underlying the dosage compensation process during early mammalian development.dosage compensation ͉ epigenetics ͉ imprinting ͉ mouse development ͉ X inactivation

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mentioning

confidence: 94%

Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

Patrat

Okamoto

Diabangouaya

et al. 2009

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

156

175

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“…1,2 XCI is a process in mammals in which one X in every XX female somatic cell is transcriptionally silenced through CpG hypermethylation and chromatin remodelling. 3 Expression of the X-inactive-specific transcript (XIST) is required for silencing. 4 The longstanding view has been that the determination of the X-chromosome to be inactivated (maternal or paternal) is random and independent in each cell.…”

Section: Introductionmentioning

confidence: 99%

Heritable skewed X-chromosome inactivation leads to haemophilia A expression in heterozygous females

et al. 2007

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Factor VIII gene, F8, mutations cause haemophilia A (HA), an X-linked recessive disorder. Expression in heterozygous females has been ascribed to skewed X-chromosome inactivation (XCI). To investigate the cause of HA in three heterozygous females within an Atlantic Canadian kindred, the proband (severely affected girl, FVIII activity: 2%) and 17 relatives across three generations were studied. F8 genotype, FVIII activity, XCI ratio (XCIR) (paternal active X: maternal active X), karyotype, submegabase resolution tiling set array competitive genome hybridization (competitive genomic hybridization (SMRT)), and microsatellite analyses were utilized. A positive linear relationship between FVIII activity and percentageactivated normal X-chromosome was found in HA heterozygous females (R 2 ¼ 0.87). All affected, but no unaffected females, had an XCIR skewed toward activation of the mutant X-chromosome (proband 92:8, SD 2). Unexpectedly, high numbers of females have dramatically skewed XCIRs (480:20 or o20:80) (Po0.05). The distribution of XCIR frequencies within this family was significantly different than predicted by normal population data or models of random XCI (Po0.025), with more females having higher degrees of skewing. Known causes of skewing, such as chromosomal abnormalities, selection against deleterious alleles, and X-inactive-specific transcript mutations, are not consistent with our results. This study shows that FVIII activity in HA heterozygous females can be directly related to XCI skewing, and that low FVIII activity in females in this family is due to unfavourable XCI skewing. Further, the findings suggest that these XCI ratios are genetically influenced, consistent with a novel heritable human X controlling element (XCE) functioning similarly to the mouse Xce.

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“…Dans cette revue, nous nous intéresserons en particulier aux mécanismes moléculaires mis en place durant cette étape. Puis, nous aborderons plus brièvement la deuxième phase d'inactivation dite « inactivation aléatoire » qui aboutit à l'inactivation, soit du Xp, soit SYNTHÈSE REVUES Résistance de l'allèle maternel à l'inactivation La létalité précoce d'embryons disomiques pour le X maternel (possédant deux Xm) ou héritant d'une délétion paternelle de Xist, probablement due à une déficience de compensation de dose, plaide pour une résistance du chromosome maternel à l'inactivation [9][10][11]. De même, des transgènes autosomiques portant la région Xic peuvent reproduire l'expression de Xist lorsqu'ils sont transmis à partir de la lignée germinale mâle alors qu'ils ne peuvent le faire lorsqu'ils sont transmis à partir de la lignée germinale femelle [8].…”

Section: Inactivation Du Chromosome X Soumise à Empreinteunclassified

“…Inconnue : empêche l'inactivation du Xm [9,12] RNF12 : active l'expression de Xist à partir de Xp [15] Empreinte paternelle ? Préinactivation du Xp [17,25] 4 .…”

Section: Empreinte(s) Maternelle(s) ?unclassified

Le modèle de l’inactivation du chromosome X chez la souris

et al. 2012

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Parental source of chromosome imprinting and its relevance for X chromosome inactivation

Cited by 85 publications

References 33 publications

Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

Heritable skewed X-chromosome inactivation leads to haemophilia A expression in heterozygous females

Le modèle de l’inactivation du chromosome X chez la souris

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