Fig. 3.
Kinetics of X-chromosome inactivation during development in mice. Stages after zygotic genome activation are represented together with a schematic view of the XCI pattern. Xist domain is depicted by a green oval. Xist, Tsix and X-linked genes expression are depicted by green, yellow and red dots, respectively. (A) Acquisition of a maternal imprint during oocyte growth and of a paternal imprint either during spermatogenesis or early after fertilization. (B) Establishment of imprinted X-chromosome inactivation (XCI). The marks on the paternal Xp are indicated along the arrow to reflect when they start to be acquired. Cot-1 exclusion refers to the absence of labelling of essentially intergenic transcripts by RNA fluorescence in situ hybridization using a Cot-1 probe. Whether the X-chromosome is preinactivated at the 2-cell stage is unresolved [75,77]. Tsix RNA is present in a fraction of cells in E3.5 blastocysts but it is not known if the expression is equivalent in the trophectoderm and the ICM. (C) Reactivation and random XCI in the embryonic lineage (blue). In the ICM of E4.5 blastocysts and in ES cells, which are derived from the ICM, the Xist domain and the heterochromatin marks on the Xp are lost and Xist and Tsix are expressed biallelically. However, Xist expression is very low and hence not represented here (Sun et al., 2006). In the epiblast after E5.5 and in differentiated ES cells, either the paternal or the maternal X-chromosome is inactivated due to random XCI. Known heterochromatin marks associated with the inactive X-chromosome are indicated. (D) Maintenance of imprinted XCI in the trophoblast (light red) and primitive endoderm (yellow) lineages. In the trophoblast lineage, the imprinted pattern of XCI is maintained without interruption. Tsix expression in the trophoblast lineage at E6.5 is inferred from its expression pattern at earlier and later stages and from its requirement on Xm early after implantation. In the primitive endoderm lineage, XCI is imprinted, but it is not known if the Xp is continuously inactive or if it is transiently reactivated when the primitive endoderm differentiates from the ICM (green question mark). Also, Tsix pattern of expression has not been reported in the primitive endoderm lineage (yellow question mark). Known marks on the Xp are indicated for TS cells [81,91,134,135] and XEN cells [91,136], which are cell models of the trophectoderm and the visceral endoderm, respectively. See text for additional references. Xp, paternal X-chromosome; Xm, maternal X-chromosome; ICM, inner cell mass; TE, trophectoderm; EPI, epiblast; EC, ectoplacental cone; EE, extraembryonic ectoderm; ES cells, embryonic stem cells; TS cells, trophoblast stem cells; XEN cells, extraembryonicextraembryonic stem cells; PRC1, Polycomb-Repressive Complex 1; PRC2, Polycomb-Repressive Complex 2.