Female mammals inactivate one of their two X-chromosomes to compensate for the difference in gene-dosage with males\r\nthat have just one X-chromosome. X-chromosome inactivation is initiated by the expression of the non-coding RNA Xist,\r\nwhich coats the X-chromosome in cis and triggers gene silencing. In early mouse development the paternal X-chromosome\r\nis initially inactivated in all cells of cleavage stage embryos (imprinted X-inactivation) followed by reactivation of the\r\ninactivated paternal X-chromosome exclusively in the epiblast precursors of blastocysts, resulting temporarily in the\r\npresence of two active X-chromosomes in this specific lineage. Shortly thereafter, epiblast cells randomly inactivate either\r\nthe maternal or the paternal X-chromosome. XCI is accompanied by the accumulation of histone 3 lysine 27 trimethylation\r\n(H3K27me3) marks on the condensed X-chromosome. It is still poorly understood how XCI is regulated during early human\r\ndevelopment. Here we have investigated lineage development and the distribution of H3K27me3 foci in human embryos\r\nderived from an in-vitro model for human implantation. In this system, embryos are co-cultured on decidualized\r\nendometrial stromal cells up to day 8, which allows the culture period to be extended for an additional two days. We\r\ndemonstrate that after the co-culture period, the inner cell masses have relatively high cell numbers and that the GATA4-\r\npositive hypoblast lineage and OCT4-positive epiblast cell lineage in these embryos have segregated. H3K27me3 foci were\r\nobserved in ,25% of the trophectoderm cells and in ,7.5% of the hypoblast cells, but not in epiblast cells. In contrast with\r\nday 8 embryos derived from the co-cultures, foci of H3K27me3 were not observed in embryos at day 5 of development\r\nderived from regular IVF-cultures. These findings indicate that the dynamics of H3K27me3 accumulation on the Xchromosome\r\nin human development is regulated in a lineage specific fashion.
Loading....