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 γ globin expression were treated with the histone deacetylase inhibitor trichostatin A (TSA). Culture of the post-switch hybrids in the presence of TSA reactivated γ globin expression and concommitantly downregulated β globin expression, as determined by both mRNA quantitation and immunofluorescent quantitation of γ globin expressing cells. In contrast, similar treatment of pre-switch hybrids, which were expressing predominantly γ globin and only small levels of β globin, had no effect on the relative γ or β globin gene expression. In addition, trichostatin A induced γ 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 β globin locus in the adult stage of development.