The histone deacetylase inhibitor, trichostatin A, reactivates the developmentally silenced γ globin expression in somatic cell hybrids and induces γ gene expression in adult BFUe cultures

Somatic cell hybrids that have undergone globin gene switching and developmental silencing of gamma globin expression were treated with the histone deacetylase inhibitor trichostatin A (TSA). Culture of the post-switch hybrids in the presence of TSA reactivated gamma globin expression and concommitantly downregulated beta globin expression, as determined by both mRNA quantitation and immunofluorescent quantitation of gamma globin expressing cells. In contrast, similar treatment of pre-switch hybrids, which were expressing predominantly gamma globin and only small levels of beta globin, had no effect on the relative gamma or beta globin gene expression. In addition, trichostatin A induced gamma gene expression in adult BFUe cultures in a maturation-independent fashion. The results provide direct evidence that inhibition of HDAC activity can alter expression from the human beta globin locus in the adult stage of development. (C) 2003 Elsevier Science (USA). All rights reserved.