Transcriptional regulation of the XXXX Liver X Receptor a gene by Hepatocyte Nuclear Factor 4a.

@entity1 @entity5907 @entity13466 @entity5068 @entity165
UNASSIGNED: Liver X Receptors (LXRs) are @entity5068 -activated transcription factors that play major roles in cellular @entity165 homeostasis, HDL biogenesis and reverse @entity165 transport. The aim of the present study was to investigate the mechanisms that control the expression of the @entity1 @entity13466 gene in hepatic cells. A series of reporter plasmids containing consecutive 5' deletions of the hLXRa promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the @entity1 @entity13466 promoter was significantly reduced by deleting the  -111 to  -42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 a ( @entity5907 ) in this area. Overexpression of @entity5907 in HEK 293T cells increased the expression of all @entity13466 promoter constructs except  -42/+384. In line, silencing the expression of endogenous @entity5907 in HepG2 cells was associated with reduced @entity13466 protein levels and reduced activity of the  -111/+384 @entity13466 promoter but not of the  -42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel @entity5907 specific binding motif (H4-SBM) in the  -50 to  -40 region of the @entity1 @entity13466 promoter. A triple mutation in this H4-SBM abolished @entity5907 binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by @entity5907 . In conclusion, our data indicate that @entity5907 may have a wider role in cell and plasma @entity165 homeostasis by controlling the expression of @entity13466 in hepatic cells.
