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Genome-wide analysis of ETS factor ER71/ETV2 chromatin occupancy

ABSTRACT: We discover that ER71/ETV2 initiates hemangiogenic program by activating blood and endothelial cell lineage specifying genes while enhancing FLK1 expression and expanding hemangioblast population. Furthermore, ER71/ETV2 establishes an ETS hierarchy by directly activating Ets genes in hematopoietic and endothelial cell lineage development. As such, ER71/ETV2-initiated blood and endothelial cell program is maintained by ER71/ETV2 downstream ETS factors through an ETS switching mechanism. ChIP-seq analysis of ER71 in differentiated embryonic stem cells

ORGANISM(S): Mus musculus

SUBMITTER: Daofeng Li

PROVIDER: E-GEOD-59402 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Induction of hematopoietic and endothelial cell program orchestrated by ETS transcription factor ER71/ETV2.

Liu Fang F Li Daofeng D Yu Yik Yeung Lawrence YY Kang Inyoung I Cha Min-Ji MJ Kim Ju Young JY Park Changwon C Watson Dennis K DK Wang Ting T Choi Kyunghee K

EMBO reports 20150323 5

The ETS factor ETV2 (aka ER71) is essential for the generation of the blood and vascular system, as ETV2 deficiency leads to a complete block in blood and endothelial cell formation and embryonic lethality in the mouse. However, the ETV2-mediated gene regulatory network and signaling governing hematopoietic and endothelial cell development are poorly understood. Here, we map ETV2 global binding sites and carry out in vitro differentiation of embryonic stem cells, and germ line and conditional kn ...[more]

PMID: 25802403

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Hemangioblast skewing from embryonic stem(ES) cells by defined factors

Project description:Successful derivation of a specific cell lineage from pluripotent stem cells will tremendously facilitate the clinical usage of pluripotent stem derived somatic cells. Herein, we demonstrate that ER71/Etv2, GATA2 and Scl form a core network in hemangioblast development and that transient co-expression of these three factors robustly induced hemangioblasts from ES cells. Such induced hemangioblasts potently generated hematopoietic and endothelial cells in culture as well as in vivo, warranting the evaluation of these cells in the future for repairing and/or regenerating hematopoietic and/or angiogenic defects. We have established a doxycycline inducible ES cell, iEGS, in which ER71/Etv2, GATA2 three transcription factors can be transiently co-expressed by doxycycline induction. We further analyzed the downstream target genes and signaling pathways at 6, 12 and 24hrs after ER71/Etv2, GATA2 induction. These data were obtained from three independent experiments.

2014-02-03 | E-GEOD-45147 | biostudies-arrayexpress

Expression data from day 3 Flk-1 mesoderm between ER71 overexpressed and ER71 knockout mouse embryonic stem cell

Project description:Ets transcription factor ER71 is critical for Flk-1 mesoderm specification to different cell lineages. In this dataset, we determine to investigate the mechanisms by which ER71 regulates hematopoietic and endothelial cell versus cardiac cell lineage development. Expression of all four Flk-1+ mesoderm populations (i.e. Er71 overexpressed versus control, Er71 deficient versus control Flk-1+ mesoderm) was compared. Specifically, we sorted Flk-1+ mesoderm from day 3 differentiated embryonic stem(ES) cells, including induced Er71 and control ES cells, as well as Er71+/+ as well as Er71-/- ES cells .

2012-02-20 | E-GEOD-35793 | biostudies-arrayexpress

Genome-wide analysis of ETS factor ER71/ETV2 chromatin occupancy

Project description:We discover that ER71/ETV2 initiates hemangiogenic program by activating blood and endothelial cell lineage specifying genes while enhancing FLK1 expression and expanding hemangioblast population. Furthermore, ER71/ETV2 establishes an ETS hierarchy by directly activating Ets genes in hematopoietic and endothelial cell lineage development. As such, ER71/ETV2-initiated blood and endothelial cell program is maintained by ER71/ETV2 downstream ETS factors through an ETS switching mechanism.

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Gene expression analysis of inducible ES cells overexpressing Etv2 (induced for 12 hours at day 3 of differentiation)

Project description:During embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages, however, the precise roles of Etv2 in yolk sac development remains unclear. We carried out a transcriptome analysis using an ES cell line that can inducibly express Etv2. Cells were induced for 12 hours at day 3 of differentiation. An ES cell line (dervied from mouse of background strain 129P2/Ola) with a doxycycline inducible expression casette of Etv2 (ER71 A2Lox.cre) was differentiated in hanging drops. At 3 days of differentiation, cells were treated with doxycycline for 12 hours, and subsequently Flk1(+) cells were sorted. Experiment was done in triplicate and untreated cells were used for control.

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Gene expression analysis of inducible ES cells overexpressing Etv2 (induced for 12 hours at day 3 of differentiation)

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ETV2/ER71 regulates hematovascular lineage generation and vascularization through an H3K9 demethylase, KDM4A

Project description:ETV2/ER71, an ETS transcription factor, is critical for hematopoiesis and vascular development. However, knowledge on the molecular mechanisms behind ETV2-mediated gene transcription is limited. Here, we show that ETV2 together with KDM4A, an H3K9 demethylase, regulates hematopoietic and endothelial genes. Etv2-/- mouse embryonic stem cells (mESCs), which fail to generate hematopoietic and endothelial cells, showed enhanced levels of H3K9me3 on hematopoietic and endothelial genes. ETV2 interacts with KDM4A and the ETV2-mediated transcriptional activation of hematopoietic and endothelial genes is dependent on KDM4A histone demethylase activity. ETV2 and KDM4A co-occupy the transcription regulatory regions of genes whose expression is directly regulated by ETV2. Mice lacking Kdm4a and Etv2 in endothelial cells (Cdh5Cre;Kdm4af/f;Etv2f/f) displayed a more severe defect in perfusion recovery and neovascularization compared with Cdh5Cre;Kdm4af/f, Cdh5Cre;Etv2f/f mice and controls. Collectively, we demonstrated that ETV2 interacts with KDM4A and that this interaction is critical for FLK1+ cell generation, differentiation into the downstream lineages, and vascular regeneration.

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ER71/ETV2-mediated direct reprogramming of human dermal fibroblasts (HDFs) into endothelial-like cells

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2013-09-12 | E-GEOD-50801 | biostudies-arrayexpress

ER71/ETV2-mediated direct reprogramming of human dermal fibroblasts (HDFs) into endothelial-like cells

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Comparison of Flk-1+/Etv2- vs Flk-1+/Etv2+ populations

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