COINDUCTION OF EMBRYONIC AND ADULT-TYPE GLOBIN MESSENGER-RNAS BY SODIUM-BUTYRATE AND TRICHOSTATIN-A IN 2 MURINE INTERLEUKIN-3-DEPENDENT BONE-MARROW-DERIVED CELL-LINES

Using an RNase protection assay, globin mRNA species expressed in clon es derived from Ba/F3 and B6SUtA cells transfected with the erythropoi etin receptor (EpoR) and selected with erythropoietin (Epo) were compa red with globin mRNA species induced in corresponding parental cells b y sodium butyrate (SB) and trichostatin A (TSA). beta(Major)/beta(mino r)- and alpha-1/alpha-2-globin mRNAs were the major species, with trac e amounts of epsilon-globin mRNA, formed in Epo-stimulated EpoR(+) Ba/ F3 clones, whereas SB and TSA allowed expression of all species of glo bin mRNAs, ie, epsilon, beta h1, beta(Major)/beta(minor), zeta, and al pha-1/alpha-2, in parental Ba/F3 cells. In contrast, epsilon- and alph a-1/alpha-2-globin mRNAs were the major species present in Epo-stimula ted EpoR(+) B6SUtA clones, whereas SB and TSA activated epsilon-, beta h1-, beta(S)/beta(T)-, and alpha-1/alpha-2-globin genes in parental B 6SUtA cells; zeta-globin mRNA was not detected in SB- and TSA-treated B6SUtA cells. Because TSA is a specific inhibitor of histone deacetyla se, the mimicry of action exhibited by SB and TSA suggests that the ef fects of SB are mediated through its ability to inhibit histone deacet ylase and that histone deacetylase is an integral part of the repressi on of globin genes in these interleukin-3-dependent cells. Efficient c oinduction 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 mo dels to study the mechanism(s) of developmental globin gene switching. (C) 1998 by The American Society of Hematology.