Nuclear receptors are important regulators of erythroid cell development. Here 
we investigated the impact of retinoid X receptor (RXR), retinoic acid receptor 
(RAR), and of the c-erbA/thyroid hormone (T3) receptor (c-erbA/TR) on growth and 
differentiation of erythroid cells using an in vitro culture system of stem cell 
factor-dependent erythroid progenitors. RXR, RAR, and c-erbA/TR-specific ligands 
were found to induce erythroid-specific gene expression and to accelerate 
erythroid differentiation in culture, with T3 being most effective. Furthermore, 
while ligand-activated c-erbA/TR accelerated differentiation, unliganded 
c-erbA/TR effectively blocked differentiation and supported sustained progenitor 
growth in culture. Thus, c-erbA/TR appears to act as a binary switch affecting 
erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated 
c-erbA/TR induces differentiation. Additionally, to determine the impact of RXR 
for erythroid cell development, dominant interfering mutant RXRs, lacking the 
transcriptional activator functions AF-1 and AF-2, or AF-2 only, or the entire 
DNA-binding domain, were introduced into erythroid progenitor cells via 
recombinant retrovirus vectors and analyzed for RXR-specific effects. It was 
found that expression of wild-type RXR and of the RXR mutants devoid of AF-1 
and/or AF-2 supported a transient outgrowth of erythroid cells. In marked 
contrast, expression of the dominant interfering deltaDNA-binding domain RXR, 
containing a deletion of the entire DNA-binding domain, was incompatible with 
erythroid cell growth in vitro, suggesting a pivotal role of RXR for erythroid 
cell development.