NDLI: Hepatocyte nuclear factor-4α interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression

Content Provider	PubMed Central
Author	Wang, Zhongyan Burke, Peter A.
Abstract	Transthyretin (TTR) is a negative acute phase protein whose serum level decreases during the acute phase response (APR). TTR gene expression in liver is regulated at the transcriptional level, and controlled by hepatocyte nuclear factor (HNF)-4α and other HNFs. The site-directed mutagenesis of the HNF-4, HNF-1, HNF-3 or HNF-6 binding sites in the TTR proximal promoter dramatically decreased TTR promoter activity. Interestingly, the mutation of HNF-4 binding site not only abolished the response to HNF-4α, but also significantly reduced the response to other HNFs. However, mutation of the HNF-4 binding site merely affected the specific binding of HNF-4α, but not other HNFs, suggesting that an intact HNF-4 binding site provides not only a platform for specific interaction with HNF-4α, but also facilitates the interaction of HNF-4α with other HNFs. In a cytokine-induced APR cell culture model, we observed a significant reduction in the binding of HNF-4α, HNF-1α, HNF-3β and HNF-6α to the TTR promoter, which correlates with the decrease in the TTR expression after injury. These findings provide a new insight into the mechanism of the negative transcriptional regulation of TTR gene after injury caused by a decrease in HNFs’ binding and a modulation in their coordinated interactions.
Related Links	http://dx.doi.org/10.1111/j.1742-4658.2010.07802.x
Ending Page	4075
Page Count	10
Starting Page	4066
File Format	PDF
ISSN	1742464X
e-ISSN	17424658
Journal	The FEBS journal
Issue Number	19
Volume Number	277
Language	English
Publisher Date	2010-10-01
Access Restriction	Open
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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