Transcriptional Coactivators CBP and p300 Cooperatively Enhance HNF-1α–Mediated Expression of the Albumin Gene in Hepatocytes

Transcriptional coactivators, CREB-binding protein (CBP) and p300, exhibit high homology in structure and similar functions. In the present study, we analyzed the function of CBP and p300 proteins as transcriptional coactivators in the expression of albumin in hepatocytes. The expression levels of C...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 2004-09, Vol.136 (3), p.313-319
Main Authors: Dohda, Takeaki, Kaneoka, Hidenori, Inayoshi, Yujin, Kamihira, Masamichi, Miyake, Katsuhide, Iijima, Shinji
Format: Article
Language:English
Subjects:
CBP
HNF-1α
p300
primary hepatocytes
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transcriptional coactivators, CREB-binding protein (CBP) and p300, exhibit high homology in structure and similar functions. In the present study, we analyzed the function of CBP and p300 proteins as transcriptional coactivators in the expression of albumin in hepatocytes. The expression levels of CBP and p300 were high in fetal hepatocytes, but low in adult ones. Immunoprecipitation assays showed that both CBP and p300 interacted with hepatocyte nuclear factor-1α (HNF-1α) in primary hepatocytes. Furthermore, CBP and p300 were co-precipitated without HNF-1α. Chromatin immunoprecipitation (ChIP) assays revealed that both CBP and p300 are located in the albumin promoter region in hepatocytes. These results suggested that HNF-1α, CBP and p300 were incorporated into a preinitiation complex of RNA polymerase II at the albumin promoter. Luciferase reporter assays showed that CBP and p300 cooperatively triggered HNF-1α–mediated transcription of the albumin promoter. In addition, inhibition of CBP or p300 using small interfering RNAs (siRNAs) resulted in a reduction in albumin expression. These results suggest that both CBP and p300 are required for enhanced expression of albumin.
ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvh123