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学科主题: Biochemistry & Molecular Biology
题名: Zebrafish mll Gene Is Essential for Hematopoiesis
作者: Wan, Xiaoyang ; Hu, Bo ; Liu, Jing-xia ; Feng, Xi ; Xiao, Wuhan
通讯作者: Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China ; w-xiao@ihb.ac.cn
关键词: PROTO-ONCOPROTEIN MLL ; HOX GENES ; ACUTE LEUKEMIAS ; STEM-CELL ; DEFINITIVE HEMATOPOIESIS ; DROSOPHILA-TRITHORAX ; 11Q23 TRANSLOCATIONS ; DNA DEMETHYLATION ; MUTANT MICE ; HISTONE
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2011
卷: 286, 期:38, 页:33345-33357
收录类别: SCI
部门归属: [Wan, XY; Hu, B; Liu, JX; Feng, X; Xiao, WH] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
资助者: National Science Foundation of China[30971667, 31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]
摘要: Studies implicate an important role for the mixed lineage leukemia (Mll) gene in hematopoiesis, mainly through maintaining Hox gene expression. However, the mechanisms underlying Mll-mediated hematopoiesis during embryogenesis remain largely unclear. Here, we investigate the role of mll during zebrafish embryogenesis, particularly hematopoiesis. Mll depletion caused severe defects in hematopoiesis as indicated by a lack of blood flow and mature blood cells as well as a significant reduction in expression of hematopoietic progenitor and mature blood cell markers. Furthermore, mll depletion prevented the differentiation of hematopoietic progenitors. In addition, we identified the N-terminal mini-peptide of Mll that acted as a dominant negative form to disrupt normal function of mll during embryogenesis. As expected, mll knockdown altered the expression of a subset of Hox genes. However, overexpression of these down-regulated Hox genes only partially rescued the blood deficiency, suggesting that mll may target additional genes to regulate hematopoiesis. In the mll morphants, microarray analysis revealed a dramatic up-regulation of gadd45 alpha a. Multiple assays indicate that mll inhibited gadd45 alpha a expression and that overexpression of gadd45 alpha a mRNA led to a phenotype similar to the one seen in the mll morphants. Taken together, these findings demonstrate that zebrafish mll plays essential roles in hematopoiesis and that gadd45 alpha a may serve as a potential downstream target for mediating the function of mll in hematopoiesis.
语种: 英语
WOS记录号: WOS:000294968800053
ISSN号: 0021-9258
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/16351
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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Recommended Citation:
Wan, Xiaoyang; Hu, Bo; Liu, Jing-xia; Feng, Xi; Xiao, Wuhan.Zebrafish mll Gene Is Essential for Hematopoiesis,JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(38):33345-33357
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