The histone deacetylase inhibitor, trichostatin A, reactivates the developmentally silenced gamma globin expression in somatic cell hybrids and induces gamma 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.
Department of Medical Genetics, University of Washington, Seattle, WA 98195, USA.
Richard A
RA
Swank
Eva
E
Skarpidi
Thalia
T
Papayannopoulou
George
G
Stamatoyannopoulos
D000328:Adult; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D020868:Gene Silencing; D005812:Genes, Switch; D005914:Globins / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D005914:Globins