title: Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α.
abstract: BACKGROUND
  Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.
  
  
  RESULTS
  The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).
  
  
  CONCLUSIONS
  The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.
authors.affiliation: Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bishop
authors.forename: Peter A
authors.initials: PA
authors.lastname: Burke
mesh_terms: D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; C494112:ELK1 protein, human; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D034741:RNA, Small Interfering; D050807:ets-Domain Protein Elk-1