TATA ELEMENT-BINDING PROTEIN IS IMPORTANT TO EPIDERMAL GROWTH FACTOR-DEPENDENT INDUCTION OF H2B HISTONE GENE-EXPRESSION IN PRIMARY HEPATOCYTES FROM RAT

Epidermal growth factor (EGF) is a potent mitogen for rat hepatocytes and mammalian histone synthesis is functionally and temporally coupled to DNA replication. To gain an insight on the role of EGF in the regu lation of H2B histone gene expression in primary hepatocyte cultures, the binding patterns of nuclear proteins to various elements in the H2 B histone gene upstream region have been investigated. EGF induced H2B histone mRNA with maximal stimulation reached at 36 hours. The induct ion of H2B histone mRNA was dependent on the concentration of EGF and almost reduced by actinomycin-D pretreatment. In DNase I footprinting analysis, one nuclear factor (TATA element-binding protein, TBP) bound at -20 bp (TATA element) in either the absence or presence of EGF. On e DNA-protein complex was formed by DNA mobility shift assay when TATA element was incubated with nuclear extract prepared from EGF-free hep atocytes, and the amount of TBP was increased after EGF treatment. The se results suggest that TBP may be correlated with transcriptional reg ulation of H2B histone gene by EGF in primary hepatocytes.