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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

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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
Subjects: Q Science > QH Natural history
Q Science > QR Microbiology
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:
DateEvent
28 July 2017Published
19 June 2017Accepted
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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