title: Cooperative interaction of Etv2 and Gata2 regulates the development of endothelial and hematopoietic lineages.
abstract: Regulatory mechanisms that govern lineage specification of the mesodermal progenitors to become endothelial and hematopoietic cells remain an area of intense interest. Both Ets and Gata factors have been shown to have important roles in the transcriptional regulation in endothelial and hematopoietic cells. We previously reported Etv2 as an essential regulator of vasculogenesis and hematopoiesis. In the present study, we demonstrate that Gata2 is co-expressed and interacts with Etv2 in the endothelial and hematopoietic cells in the early stages of embryogenesis. Our studies reveal that Etv2 interacts with Gata2 in vitro and in vivo. The protein-protein interaction between Etv2 and Gata2 is mediated by the Ets and Gata domains. Using the embryoid body differentiation system, we demonstrate that co-expression of Gata2 augments the activity of Etv2 in promoting endothelial and hematopoietic lineage differentiation. We also identify Spi1 as a common downstream target gene of Etv2 and Gata2. We provide evidence that Etv2 and Gata2 bind to the Spi1 promoter in vitro and in vivo. In summary, we propose that Gata2 functions as a cofactor of Etv2 in the transcriptional regulation of mesodermal progenitors during embryogenesis.
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jai
authors.initials: J
authors.lastname: Richard
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Zirbes
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Wuming
authors.initials: W
authors.lastname: Gong
authors.affiliation: Stem Cell Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Gufa
authors.initials: G
authors.lastname: Lin
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: Morgridge Institute for Research, 330N. Orchard St., Madison, WI 53715, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.affiliation: Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, MN, USA. Electronic address: garry@umn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D050989:GATA2 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C503994:ER71 protein, mouse; C494712:Gata2 protein, mouse
keywords: Endothelial cell; Etv2; Gata2; Hematopoietic cell