Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation.
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. I...
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Public Library of Science (PLoS)
2012-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3296731?pdf=render |
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author | Gijs Teklenburg Charlotte H E Weimar Bart C J M Fauser Nick Macklon Niels Geijsen Cobi J Heijnen Susana M Chuva de Sousa Lopes Ewart W Kuijk |
author_facet | Gijs Teklenburg Charlotte H E Weimar Bart C J M Fauser Nick Macklon Niels Geijsen Cobi J Heijnen Susana M Chuva de Sousa Lopes Ewart W Kuijk |
author_sort | Gijs Teklenburg |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-0ad0cfa30b7a42f4a6e3dfb568287ca12022-12-21T17:25:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3270110.1371/journal.pone.0032701Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation.Gijs TeklenburgCharlotte H E WeimarBart C J M FauserNick MacklonNiels GeijsenCobi J HeijnenSusana M Chuva de Sousa LopesEwart W KuijkFemale 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.http://europepmc.org/articles/PMC3296731?pdf=render |
spellingShingle | Gijs Teklenburg Charlotte H E Weimar Bart C J M Fauser Nick Macklon Niels Geijsen Cobi J Heijnen Susana M Chuva de Sousa Lopes Ewart W Kuijk Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. PLoS ONE |
title | Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. |
title_full | Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. |
title_fullStr | Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. |
title_full_unstemmed | Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. |
title_short | Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation. |
title_sort | cell lineage specific distribution of h3k27 trimethylation accumulation in an in vitro model for human implantation |
url | http://europepmc.org/articles/PMC3296731?pdf=render |
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