Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis | |
Hu, Bo; Zhang, Wei; Feng, Xi; Ji, Wei; Xie, Xunwei; Xiao, Wuhan; Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China. | |
2014-04-01 | |
Source Publication | DEVELOPMENTAL BIOLOGY
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ISSN | 0012-1606 |
Volume | 388Issue:1Pages:81-93 |
Abstract | 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.; 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. |
Subtype | Article |
Keyword | Eafl Foxo3b Gata1 Spi1 Hematopoiesis |
Department | [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 |
DOI | 10.1016/j.ydbio.2014.01.005 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Funding Organization | NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Developmental Biology |
WOS Subject | Developmental Biology |
WOS ID | WOS:000333378200008 |
WOS Keyword | STEM-CELLS ; ERYTHROID-DIFFERENTIATION ; DEFINITIVE HEMATOPOIESIS ; STEM/PROGENITOR CELLS ; EARLY MACROPHAGES ; C-MYB ; PROMOTER ; PU.1 ; GENE ; ELL |
Funding Organization | NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] ; NSFC Grant [91019008, 31071212]; CAS Major Scientific and Technological Project [XDA08010208]; [2010CB126306] |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/342005/20089 |
Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
Corresponding Author | Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China. |
Affiliation | Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China |
Recommended Citation GB/T 7714 | Hu, Bo,Zhang, Wei,Feng, Xi,et al. Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis[J]. DEVELOPMENTAL BIOLOGY,2014,388(1):81-93. |
APA | Hu, Bo.,Zhang, Wei.,Feng, Xi.,Ji, Wei.,Xie, Xunwei.,...&Xiao, WH .(2014).Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis.DEVELOPMENTAL BIOLOGY,388(1),81-93. |
MLA | Hu, Bo,et al."Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis".DEVELOPMENTAL BIOLOGY 388.1(2014):81-93. |
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