抄録
Transcriptional coactivators, CREB-binding protein (CBP) and p 300, exhibit high homology in structure and similar functions. In the present study, we analyzed the function of CBP and p 300 proteins as transcriptional coactivators in the expression of albumin in hepatocytes. The expression levels of CBP and p 300 were high in fetal hepatocytes, but low in adult ones. Immunoprecipitation assays showed that both CBP and p 300 interacted with hepatocyte nuclear factor-1 α (HNF-1 α) in primary hepatocytes. Furthermore, CBP and p 300 were co-precipitated without HNF-1 α, Chromatin immunoprecipitation (ChIP) assays revealed that both CBP and p 300 are located in the albumin promoter region in hepatocytes. These results suggested that HNF-1 α, CBP and p 300 were incorporated into a preinitiation complex of RNA polymerase II at the albumin promoter. Luciferase reporter assays showed that CBP and p 300 cooperatively triggered HNF-1 α-mediated transcription of the albumin pro-moter. In addition, inhibition of CBP or p 300 using small interfering RNAs (siRNAs) resulted in a reduction in albumin expression. These results suggest that both CBP and p 300 are required for enhanced expression of albumin.
