Hepatocyte nuclear factor 4alpha enhances the hepatocyte nuclear factor 1alpha-mediated activation of transcription.
Hepatocyte Nuclear Factor 1alpha (HNF1alpha) and Hepatocyte Nuclear Factor 4alpha (HNF4alpha) are two liver-enriched transcription factors coexpressed in specific tissues where they play a crucial role through their involvement in a complex cross-regulatory network. HNF1alpha down regulates HNF4alpha-mediated activation of transcription via a direct protein-protein interaction. Here we show that HNF4alpha enhances the transcriptional activity of HNF1alpha in a DNA binding independent manner, thus indicating that it behaves as a HNF1alpha coactivator. Using mutations in the ligand binding domain (LBD) of HNF4alpha, we confirmed the involvement of the Activation Function 2 module and demonstrated the requirement of the integrity of the LBD for the interaction with HNF1alpha. Moreover, we show that HNF4alpha cooperates with p300 to achieve the highest HNF1alpha-mediated transcription rates. Our findings highlight a new way by which HNF4alpha can regulate gene expression and extend our knowledge of the complexity of the transcriptional network involving HNF4alpha and HNF1alpha.
Eeckhoute
J
J
INSERM Unit 459, Laboratoire de Biologie Cellulaire, Faculté de Médecine H. Warembourg, 1 Place de Verdun, F 59045 Lille, France.
Formstecher
P
P
Laine
B
B
D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1