Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis

Abstract Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the prese...

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Autores principales:	Bhairab N. Singh, Wuming Gong, Satyabrata Das, Joshua W. M. Theisen, Javier E. Sierra-Pagan, Demetris Yannopoulos, Erik Skie, Pruthvi Shah, Mary G. Garry, Daniel J. Garry
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eda0d5c70def493b993477499d9dd848
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spelling	oai:doaj.org-article:eda0d5c70def493b993477499d9dd8482021-12-02T16:08:44ZEtv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis10.1038/s41598-019-45841-52045-2322https://doaj.org/article/eda0d5c70def493b993477499d9dd8482019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45841-5https://doaj.org/toc/2045-2322Abstract Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4 and Ccne1 as early as 6 h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP + cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream transcriptional regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.Bhairab N. SinghWuming GongSatyabrata DasJoshua W. M. TheisenJavier E. Sierra-PaganDemetris YannopoulosErik SkiePruthvi ShahMary G. GarryDaniel J. GarryNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bhairab N. Singh Wuming Gong Satyabrata Das Joshua W. M. Theisen Javier E. Sierra-Pagan Demetris Yannopoulos Erik Skie Pruthvi Shah Mary G. Garry Daniel J. Garry Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
description	Abstract Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4 and Ccne1 as early as 6 h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP + cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream transcriptional regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.
format	article
author	Bhairab N. Singh Wuming Gong Satyabrata Das Joshua W. M. Theisen Javier E. Sierra-Pagan Demetris Yannopoulos Erik Skie Pruthvi Shah Mary G. Garry Daniel J. Garry
author_facet	Bhairab N. Singh Wuming Gong Satyabrata Das Joshua W. M. Theisen Javier E. Sierra-Pagan Demetris Yannopoulos Erik Skie Pruthvi Shah Mary G. Garry Daniel J. Garry
author_sort	Bhairab N. Singh
title	Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
title_short	Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
title_full	Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
title_fullStr	Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
title_full_unstemmed	Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
title_sort	etv2 transcriptionally regulates yes1 and promotes cell proliferation during embryogenesis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/eda0d5c70def493b993477499d9dd848
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Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis

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