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Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
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Nelson, A. C. (Andrew Christopher), Mould, Arne W., Bikoff, Elizabeth K. and Robertson, Elizabeth J. (2017) Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation. Scientific Reports, 7 (1). 6793. doi:10.1038/s41598-017-06859-9
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Official URL: http://dx.doi.org/10.1038/s41598-017-06859-9
Abstract
Trophoblast stem cells (TSCs) give rise to specialized cell types within the placenta. However, the regulatory mechanisms that guide trophoblast cell fate decisions during placenta development remain ill defined. Here we exploited ATAC-seq and transcriptional profiling strategies to describe dynamic changes in gene expression and chromatin accessibility during TSC differentiation. We detect significantly increased chromatin accessibility at key genes upregulated as TSCs exit from the stem cell state. However, downregulated gene expression is not simply due to the loss of chromatin accessibility in proximal regions. Additionally, transcriptional targets recognized by the zinc finger transcriptional repressor Prdm1/Blimp1, an essential regulator of placenta development, were identified in ChIP-seq experiments. Comparisons with previously reported ChIP-seq datasets for primordial germ cell-like cells and E18.5 small intestine, combined with functional annotation analysis revealed that Blimp1 has broadly shared as well as cell type-specific functional activities unique to the trophoblast lineage. Importantly, Blimp1 not only silences TSC gene expression but also prevents aberrant activation of divergent developmental programmes. Overall the present study provides new insights into the chromatin landscape and Blimp1-dependent regulatory networks governing trophoblast gene expression.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QH Natural history Q Science > QR Microbiology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Chromatin, Trophoblast, Placenta, Stem cells | ||||||
| Journal or Publication Title: | Scientific Reports | ||||||
| Publisher: | Nature Publishing Group | ||||||
| ISSN: | 2045-2322 | ||||||
| Official Date: | 28 July 2017 | ||||||
| Dates: |
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| Date of first compliant deposit: | 16 August 2017 | ||||||
| Volume: | 7 | ||||||
| Number: | 1 | ||||||
| Article Number: | 6793 | ||||||
| DOI: | 10.1038/s41598-017-06859-9 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Publisher Statement: | ** From PubMed via Jisc Publications Router. ** History: ** received: 04-04-2017 ** accepted: 19-06-2017 | ||||||
| Access rights to Published version: | Open Access | ||||||
| Funder: | Wellcome Trust (London, England) | ||||||
| Grant number: | Grant 090532/Z/09/Z, Grant 102811 (Wellcome Trust (London, England)), |
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