Zebrafish mll Gene Is Essential for Hematopoiesis
文献类型：期刊论文
| 作者 | Wan, Xiaoyang; Hu, Bo; Liu, Jing-xia; Feng, Xi; Xiao, Wuhan |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2011-09-23 |
| 卷号 | 286期号:38页码:33345-33357 |
| 关键词 | PROTO-ONCOPROTEIN MLL HOX GENES ACUTE LEUKEMIAS STEM-CELL DEFINITIVE HEMATOPOIESIS DROSOPHILA-TRITHORAX 11Q23 TRANSLOCATIONS DNA DEMETHYLATION MUTANT MICE HISTONE |
| ISSN号 | 0021-9258 |
| 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 |
| 中文摘要 | 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. |
| 英文摘要 | 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. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | PROTO-ONCOPROTEIN MLL ; HOX GENES ; 11Q23 TRANSLOCATIONS ; ACUTE LEUKEMIAS ; STEM-CELL ; DEFINITIVE HEMATOPOIESIS ; DROSOPHILA-TRITHORAX ; DNA DEMETHYLATION ; MUTANT MICE ; HISTONE |
| 收录类别 | SCI |
| 资助信息 | National Science Foundation of China[30971667, 31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B] |
| 语种 | 英语 |
| WOS记录号 | WOS:000294968800053 |
| 公开日期 | 2011-11-09 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/16351]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wan, Xiaoyang,Hu, Bo,Liu, Jing-xia,et al. Zebrafish mll Gene Is Essential for Hematopoiesis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(38):33345-33357. |
| APA | Wan, Xiaoyang,Hu, Bo,Liu, Jing-xia,Feng, Xi,&Xiao, Wuhan.(2011).Zebrafish mll Gene Is Essential for Hematopoiesis.JOURNAL OF BIOLOGICAL CHEMISTRY,286(38),33345-33357. |
| MLA | Wan, Xiaoyang,et al."Zebrafish mll Gene Is Essential for Hematopoiesis".JOURNAL OF BIOLOGICAL CHEMISTRY 286.38(2011):33345-33357. |
入库方式： OAI收割
来源：水生生物研究所
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