A histone deacetylase inhibitor potentiates estrogen receptor activation of a stably integrated vitellogenin promoter in HepG2 cells

To compare the role of histone deactylation in estrogen activation of a tra nsiently transfected vitellogenin (VIT) promoter and an integrated VIT prom oter in the same cells, we produced three HepG2, human hepatoma, cell lines (HepG2ERV cells) stably expressing human estrogen receptor alpha (hER alph a) and containing an integrated VIT promoter-chloramphenicol acetyltransfer ase (VIT-CAT) reporter gene. The three ER-positive HepG2ERV cell lines and wild-type, ER-negative, HepG2 cells cotransfected with cytomegalovirus-hER alpha exhibited similar MOX-dependent inductions of 20- to 50-fold with a t ransiently transfected VIT-luciferase reporter and 15- to 50-fold with a tr ansfected 4-estrogen response element-TATA-luciferase reporter gene. The hi stone deacetylase inhibitor, trichostatin A, did not enhance MOX induction of the transiently transfected VIT promoter in the HepG2ERV cells. In contr ast, trichostatin A dramatically potentiated MOX induction of the stably in tegrated VIT-CAT reporter gene, resulting in MOX-ER-dependent increases in CAT activity of up to 600-fold. These data demonstrate that although ligand ed ER exhibits the capacity to fully activate a transiently transfected VIT promoter, under some circumstances the ability to reorganize a repressive chromatin structure may be limiting for steroid receptor action.