An in vitro globin gene switching model based on differentiated embryonic stem cells.

We used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro. We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation, a switch occurs to the fetal/adult genes. In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies. We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development. When the human epsilon- or beta-globin genes driven by the dominant control region (DCR) are introduced into this system, the human epsilon-globin gene, in contrast to the beta-globin gene, is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene. We conclude from this that the epsilon-globin gene is not regulated by competition with other genes in the human beta-globin locus.