Published online 11 May 2004
Nucleic Acids Research, 2004, Vol. 32, No. 8 2586-2593
© 2004 Oxford University Press
Hepatocyte Nuclear Factor 4
enhances the Hepatocyte Nuclear Factor 1-mediated activation of transcription
INSERM Unit 459, Laboratoire de Biologie Cellulaire, Faculté de Médecine H. Warembourg, 1 Place de Verdun, F 59045 Lille, France
*To whom correspondence should be addressed. Tel: +33 3 20 62 69 51; Fax: +33 3 20 62 68 84; Email: blaine{at}lille.inserm.fr
Received March 2, 2004; Revised April 2, 2004; Accepted April 13, 2004
Hepatocyte Nuclear Factor 1
(HNF1) and Hepatocyte Nuclear Factor 4 (HNF4) 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. HNF1 down regulates HNF4-mediated activation of transcription via a direct protein–protein interaction. Here we show that HNF4 enhances the transcriptional activity of HNF1 in a DNA binding independent manner, thus indicating that it behaves as a HNF1 coactivator. Using mutations in the ligand binding domain (LBD) of HNF4, we confirmed the involvement of the Activation Function 2 module and demonstrated the requirement of the integrity of the LBD for the interaction with HNF1. Moreover, we show that HNF4 cooperates with p300 to achieve the highest HNF1-mediated transcription rates. Our findings highlight a new way by which HNF4 can regulate gene expression and extend our knowledge of the complexity of the transcriptional network involving HNF4 and HNF1.
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