title: Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation.
abstract: Female mammals inactivate one of their two X-chromosomes to compensate for the difference in gene-dosage with males that have just one X-chromosome. X-chromosome inactivation is initiated by the expression of the non-coding RNA Xist, which coats the X-chromosome in cis and triggers gene silencing. In early mouse development the paternal X-chromosome is initially inactivated in all cells of cleavage stage embryos (imprinted X-inactivation) followed by reactivation of the inactivated paternal X-chromosome exclusively in the epiblast precursors of blastocysts, resulting temporarily in the presence of two active X-chromosomes in this specific lineage. Shortly thereafter, epiblast cells randomly inactivate either the maternal or the paternal X-chromosome. XCI is accompanied by the accumulation of histone 3 lysine 27 trimethylation (H3K27me3) marks on the condensed X-chromosome. It is still poorly understood how XCI is regulated during early human development. Here we have investigated lineage development and the distribution of H3K27me3 foci in human embryos derived from an in-vitro model for human implantation. In this system, embryos are co-cultured on decidualized endometrial stromal cells up to day 8, which allows the culture period to be extended for an additional two days. We demonstrate that after the co-culture period, the inner cell masses have relatively high cell numbers and that the GATA4-positive hypoblast lineage and OCT4-positive epiblast cell lineage in these embryos have segregated. H3K27me3 foci were observed in ∼25% of the trophectoderm cells and in ∼7.5% of the hypoblast cells, but not in epiblast cells. In contrast with day 8 embryos derived from the co-cultures, foci of H3K27me3 were not observed in embryos at day 5 of development derived from regular IVF-cultures. These findings indicate that the dynamics of H3K27me3 accumulation on the X-chromosome in human development is regulated in a lineage specific fashion.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: Teklenburg
authors.forename: Charlotte H E
authors.initials: CH
authors.lastname: Weimar
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Nick
authors.initials: N
authors.lastname: Macklon
authors.forename: Niels
authors.initials: N
authors.lastname: Geijsen
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
authors.forename: Ewart W
authors.initials: EW
authors.lastname: Kuijk
mesh_terms: D001755:Blastocyst / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000378:metabolism; D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology; D010064:Embryo Implantation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D049951:X Chromosome Inactivation
chemical_list: D006657:Histones