Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1093-1103 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 30 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 16 Mar 2011 |
Keywords
- gata1
- haematopoiesis
- lineage fate decisions
- pu.1
- tif1γ
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Neuroscience(all)