Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis.
Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis.
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DOI：
10.1016/j.ydbio.2014.01.005
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发表时间：
2014-04
影响因子：
2.7
通讯作者：
Bo Hu;Wei Zhang;Xi Feng;W. Ji;Xunwei Xie;Wuhan Xiao
中科院分区：
文献类型：
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作者：
Bo Hu;Wei Zhang;Xi Feng;W. Ji;Xunwei Xie;Wuhan Xiao
Studies implicate a potential role forEAF1in MLL–ELL induced leukemogenesis; however the biological function ofEAF1in this process remains unknown. In this study, we show that knockdown of zebrafisheaf1by morpholinos caused serious defects in both primitive and definitive hematopoiesis. Using microarray analysis, we identifiedfoxo3bas a target gene suppressed byeaf1. Ectopic expression offoxo3bin embryos mimicked the phenotypes exhibited ineaf1morphants, except thatfoxo3bhad no effect onrunx1andc-mybexpression whileeaf1morphants did not express these markers in the ventral wall of dorsal aorta. Subsequent experiments showed that a dominant negative form of Foxo3b (dn-foxo3b) partially restored primitive hematopoietic defects ineaf1morphants, suggesting thatfoxo3bmight serve as a key factor for mediatingeaf1function in primitive hematopoiesis. Furthermore, we observed thatfoxo3binhibited the transcriptional activity ofgata1andspi1through protein–protein interaction. Our findings not only suggest a function ofeaf1on hematopoiesisin vivo, but also reveal a novel regulatory pathway,eaf1–foxo3b–gata1/spi1, that may shed light on the role ofEAF1in MLL–ELL induced leukemogenesis.
