Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation

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 describ...

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Autores principales:	Andrew C. Nelson, Arne W. Mould, Elizabeth K. Bikoff, Elizabeth J. Robertson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/26d028b01be84c588d0195e0202b97a3
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spelling	oai:doaj.org-article:26d028b01be84c588d0195e0202b97a32021-12-02T16:07:01ZMapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation10.1038/s41598-017-06859-92045-2322https://doaj.org/article/26d028b01be84c588d0195e0202b97a32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06859-9https://doaj.org/toc/2045-2322Abstract 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.Andrew C. NelsonArne W. MouldElizabeth K. BikoffElizabeth J. RobertsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrew C. Nelson Arne W. Mould Elizabeth K. Bikoff Elizabeth J. Robertson Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
description	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.
format	article
author	Andrew C. Nelson Arne W. Mould Elizabeth K. Bikoff Elizabeth J. Robertson
author_facet	Andrew C. Nelson Arne W. Mould Elizabeth K. Bikoff Elizabeth J. Robertson
author_sort	Andrew C. Nelson
title	Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
title_short	Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
title_full	Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
title_fullStr	Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
title_full_unstemmed	Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation
title_sort	mapping the chromatin landscape and blimp1 transcriptional targets that regulate trophoblast differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/26d028b01be84c588d0195e0202b97a3
work_keys_str_mv	AT andrewcnelson mappingthechromatinlandscapeandblimp1transcriptionaltargetsthatregulatetrophoblastdifferentiation AT arnewmould mappingthechromatinlandscapeandblimp1transcriptionaltargetsthatregulatetrophoblastdifferentiation AT elizabethkbikoff mappingthechromatinlandscapeandblimp1transcriptionaltargetsthatregulatetrophoblastdifferentiation AT elizabethjrobertson mappingthechromatinlandscapeandblimp1transcriptionaltargetsthatregulatetrophoblastdifferentiation
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Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation

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