title: OVOL2 is a critical regulator of ER71/ETV2 in generating FLK1+, hematopoietic, and endothelial cells from embryonic stem cells.
abstract: In this study, we report that OVOL2, a C2H2 zinc finger protein, is a novel binding protein of ER71, which is a critical transcription factor for blood and vessel development. OVOL2 directly interacted with ER71, but not with ETS1 or ETS2, in the nucleus. ER71-mediated activation of the Flk1 promoter was further enhanced by OVOL2, although OVOL2 alone failed to activate it. Consistently, coexpression of ER71 and OVOL2 in differentiating embryonic stem cells led to a significant augmentation of FLK1(+), endothelial, and hematopoietic cells. Such cooperative effects were impaired by the short hairpin RNA-mediated inhibition of Ovol2. Collectively, we show that ER71 directly interacts with OVOL2 and that such interaction is critical for FLK1(+) cell generation and their differentiation into downstream cell lineages.
authors.affiliation: Department of Pediatrics, Center for Cardiovascular Biology, Emory University School of Medicine, Atlanta, GA; Department of Pharmacology, College of Medicine, University of Illinois, Chicago, IL;
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Oral Pharmacology, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea;
authors.forename: Ra Ham
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, University of Illinois, Chicago, IL;
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Oral Pharmacology, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea;
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Oral Pharmacology, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea;
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO;
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Huh
authors.affiliation: Department of Pediatrics, Center for Cardiovascular Biology, Emory University School of Medicine, Atlanta, GA;
authors.forename: Se-Yeong
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN;
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.affiliation: Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan; and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO;
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
authors.affiliation: Department of Oral Pharmacology, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea;
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.affiliation: Department of Pediatrics, Center for Cardiovascular Biology, Emory University School of Medicine, Atlanta, GA; Department of Pharmacology, College of Medicine, University of Illinois, Chicago, IL;
authors.forename: Changwon
authors.initials: C
authors.lastname: Park
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D040901:Proteomics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C503994:ER71 protein, mouse; C491431:MOVO protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2