Coinduction of embryonic and adult-type globin mRNAs by sodium butyrate and trichostatin A in two murine interleukin-3-dependent bone marrow-derived cell lines.

Using an RNase protection assay, globin mRNA species expressed in clones derived from Ba/F3 and B6SUtA cells transfected with the erythropoietin receptor (EpoR) and selected with erythropoietin (Epo) were compared with globin mRNA species induced in corresponding parental cells by sodium butyrate (SB) and trichostatin A (TSA). betaMajor/betaminor- and -1/-2-globin mRNAs were the major species, with trace amounts of epsilon-globin mRNA, formed in Epo-stimulated EpoR+ Ba/F3 clones, whereas SB and TSA allowed expression of all species of globin mRNAs, ie, epsilon, betah1, betamajor/betaminor, zeta, and -1/-2, in parental Ba/F3 cells. In contrast, epsilon- and -1/-2-globin mRNAs were the major species present in Epo-stimulated EpoR+ B6SUtA clones, whereas SB and TSA activated epsilon-, betah1-, betaS/betaT-, and -1/-2-globin genes in parental B6SUtA cells; zeta-globin mRNA was not detected in SB- and TSA-treated B6SUtA cells. Because TSA is a specific inhibitor of histone deacetylase, the mimicry of action exhibited by SB and TSA suggests that the effects of SB are mediated through its ability to inhibit histone deacetylase and that histone deacetylase is an integral part of the repression of globin genes in these interleukin-3-dependent cells. Efficient coinduction of embryonic and adult types of globin mRNA in bone marrow cell lines derived from adult mice indicates that adult hematopoietic precursors possess an embryonic nature. These cell lines are useful models to study the mechanism(s) of developmental globin gene switching.