期刊
EMBO JOURNAL
卷 30, 期 6, 页码 1093-1103出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2011.34
关键词
gata1; haematopoiesis; lineage fate decisions; pu.1; tif1 gamma
资金
- European Union
- MRC
- Medical Research Council [G1000801a] Funding Source: researchfish
Lineage fate decisions underpin much of development as well as tissue homeostasis in the adult. A mechanistic paradigm for such decisions is the erythroid versus myeloid fate decision controlled by cross-antagonism between gata1 and pu.1 transcription factors. In this study, we have systematically tested this paradigm in blood-producing populations in zebrafish embryos, including the haematopoietic stem cells (HSCs), and found that it takes a different form in each population. In particular, gata1 activity varies from autostimulation to autorepression. In addition, we have added a third member to this regulatory kernel, tif1 gamma (transcription intermediate factor-1 gamma). We show that tif1 gamma modulates the erythroid versus myeloid fate outcomes from HSCs by differentially controlling the levels of gata1 and pu.1. By contrast, tif1 gamma positively regulates both gata1 and pu. 1 in primitive erythroid and prodefinitive erythromyeloid progenitors. We therefore conclude that the gata1/pu.1 paradigm for lineage decisions takes different forms in different cellular contexts and is modulated by tif1 gamma. The EMBO Journal (2011) 30, 1093-1103. doi:10.1038/emboj.2011.34; Published online 18 February 2011
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