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 transiently transfected vitellogenin (VIT) promoter and an integrated VIT promoter in the same cells, we produced three HepG2, human hepatoma, cell lines (HepG2ERV cells) stably expressing human estrogen receptor alpha (hERalpha) and containing an integrated VIT promoter-chloramphenicol acetyltransferase (VIT-CAT) reporter gene. The three ER-positive HepG2ERV cell lines and wild-type, ER-negative, HepG2 cells cotransfected with cytomegalovirus-hERalpha exhibited similar MOX-dependent inductions of 20- to 50-fold with a transiently transfected VIT-luciferase reporter and 15- to 50-fold with a transfected 4-estrogen response element-TATA-luciferase reporter gene. The histone deacetylase inhibitor, trichostatin A, did not enhance MOX induction of the transiently transfected VIT promoter in the HepG2ERV cells. In contrast, trichostatin A dramatically potentiated MOX induction of the stably integrated VIT-CAT reporter gene, resulting in MOX-ER-dependent increases in CAT activity of up to 600-fold. These data demonstrate that although liganded 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.
Mao
C
C
Department of Biochemistry, University of Illinois, Urbana 61801, USA.
Shapiro
D J
DJ
D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014819:Vitellogenins / Q000235:genetics*
D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011960:Receptors, Estrogen; D014819:Vitellogenins; C012589:trichostatin A; D004997:Ethinyl Estradiol; D004958:Estradiol; C011310:moxestrol; D015500:Chloramphenicol O-Acetyltransferase