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题名: Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis
作者: Hu, Bo1; Zhang, Wei1; Feng, Xi1; Ji, Wei1; Xie, Xunwei1; Xiao, Wuhan1
通讯作者: Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China.
关键词: eafl ; foxo3b ; gata1 ; spi1 ; Hematopoiesis
刊名: DEVELOPMENTAL BIOLOGY
发表日期: 2014-04-01
DOI: 10.1016/j.ydbio.2014.01.005
卷: 388, 期:1, 页:81-93
收录类别: SCI
文章类型: Article
部门归属: [Hu, Bo; Zhang, Wei; Feng, Xi; Ji, Wei; Xie, Xunwei; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306]
类目[WOS]: Developmental Biology
研究领域[WOS]: Developmental Biology
摘要: Studies implicate a potential role for EAF1 in MLL-ELL induced leukemogenesis; however the biological function of EAF1 in this process remains unknown. In this study, we show that knockdown of zebrafish eaf1 by morpholinos caused serious defects in both primitive and definitive hematopoiesis. Using microarray analysis, we identified foxo3b as a target gene suppressed by eaf1. Ectopic expression of foxo3b in embryos mimicked the phenotypes exhibited in eafl morphants, except that foxo3b had no effect on runxl and c-myb expression while eaf1 morphants did not express these markers in the ventral wall of dorsal aorta. Subsequent experiments showed that a dominant negative form of Foxo3b (dnfoxo3b) partially restored primitive hematopoietic defects in eafl morphants, suggesting that foxo3b might serve as a key factor for mediating eafl function in primitive hematopoiesis. Furthermore, we observed that foxo3b inhibited the transcriptional activity of gata1 and spi1 through protein-protein interaction. Our findings not only suggest a function of eafl on hematopoiesis in vivo, but also reveal a novel regulatory pathway, eaf1-foxo3b-gata1/spi1, that may shed light on the role of EAF1 in MLL-ELL induced leukemogenesis. (C) 2014 Elsevier Inc. All rights reserved.
英文摘要: Studies implicate a potential role for EAF1 in MLL-ELL induced leukemogenesis; however the biological function of EAF1 in this process remains unknown. In this study, we show that knockdown of zebrafish eaf1 by morpholinos caused serious defects in both primitive and definitive hematopoiesis. Using microarray analysis, we identified foxo3b as a target gene suppressed by eaf1. Ectopic expression of foxo3b in embryos mimicked the phenotypes exhibited in eafl morphants, except that foxo3b had no effect on runxl and c-myb expression while eaf1 morphants did not express these markers in the ventral wall of dorsal aorta. Subsequent experiments showed that a dominant negative form of Foxo3b (dnfoxo3b) partially restored primitive hematopoietic defects in eafl morphants, suggesting that foxo3b might serve as a key factor for mediating eafl function in primitive hematopoiesis. Furthermore, we observed that foxo3b inhibited the transcriptional activity of gata1 and spi1 through protein-protein interaction. Our findings not only suggest a function of eafl on hematopoiesis in vivo, but also reveal a novel regulatory pathway, eaf1-foxo3b-gata1/spi1, that may shed light on the role of EAF1 in MLL-ELL induced leukemogenesis. (C) 2014 Elsevier Inc. All rights reserved.
关键词[WOS]: STEM-CELLS ; ERYTHROID-DIFFERENTIATION ; DEFINITIVE HEMATOPOIESIS ; STEM/PROGENITOR CELLS ; EARLY MACROPHAGES ; C-MYB ; PROMOTER ; PU.1 ; GENE ; ELL
语种: 英语
WOS记录号: WOS:000333378200008
ISSN号: 0012-1606
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20089
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China

Recommended Citation:
Hu, Bo; Zhang, Wei; Feng, Xi; Ji, Wei; Xie, Xunwei; Xiao, Wuhan.Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis,DEVELOPMENTAL BIOLOGY,2014,388(1):81-93
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