The gata1/pu.1 lineage fate paradigm varies between blood populations and is modulated by tif1γ

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  • Weatherall Institute of Molecular Medicine


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, tif1β 3 (transcription intermediate factor-1γ 3). We show that tif1β 3 modulates the erythroid versus myeloid fate outcomes from HSCs by differentially controlling the levels of gata1 and pu.1. By contrast, tif1γ 3 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 tif1γ 3.


Original languageEnglish
Pages (from-to)1093-1103
Number of pages11
JournalEMBO Journal
Issue number6
Publication statusPublished - 16 Mar 2011


  • gata1, haematopoiesis, lineage fate decisions, pu.1, tif1γ