fig1

Figure 1. X chromosome state in mouse and human female embryos. (A) Schematic of early developmental stages; (B) in mouse embryos, both X chromosomes are transcribed upon the zygote genome activation (ZGA) at 2-cell stage. Imprinted inactivation of the paternal X chromosome then takes place at the 4-cell stage and is followed by reactivation in the epiblast that will give rise to the embryo proper. Upon implantation, the epiblast undergoes random XCI whereas imprinted XCI is maintained in extraembryonic lineages. As depicted, mouse Xi is characterized by the expression and coating of Xist, whereas the Xa expresses Tsix, a long non-coding RNA that antagonizes Xist and functions specifically in mouse but not in human; (C) in human embryos, the two X chromosomes are transcribed upon ZGA at 4-cell stage and remain transcriptionally active throughout pre-implantation development. XIST and another human-specific long non-coding RNA, XACT, coat both active X chromosomes in human embryos. Notably, XIST RNA does not tightly localize on the X chromosomes but shows a diffuse pattern and its coating is not accompanied by enrichment of H3K27me3. H3K27me3 enrichment is instead observed along the Xi upon XCI initiation. XCI: X chromosome inactivation; Xi: inactive X chromosome; Xa: active X chromosome; PGC: primordial germ cell