Hepatocyte nuclear factor 4α enhances the hepatocyte nuclear factor 1α‐mediated activation of transcription

J Eeckhoute, P Formstecher, B Laine - Nucleic acids research, 2004 - academic.oup.com
J Eeckhoute, P Formstecher, B Laine
Nucleic acids research, 2004academic.oup.com
Abstract Hepatocyte Nuclear Factor 1α (HNF1α) and Hepatocyte Nuclear Factor 4α (HNF4α)
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. HNF1α down
regulates HNF4α‐mediated activation of transcription via a direct protein–protein interaction.
Here we show that HNF4α enhances the transcriptional activity of HNF1α in a DNA binding
independent manner, thus indicating that it behaves as a HNF1α coactivator. Using …
Abstract
Hepatocyte Nuclear Factor 1α (HNF1α) and Hepatocyte Nuclear Factor 4α (HNF4α) 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. HNF1α down regulates HNF4α‐mediated activation of transcription via a direct protein–protein interaction. Here we show that HNF4α enhances the transcriptional activity of HNF1α in a DNA binding independent manner, thus indicating that it behaves as a HNF1α coactivator. Using mutations in the ligand binding domain (LBD) of HNF4α, we confirmed the involvement of the Activation Function 2 module and demonstrated the requirement of the integrity of the LBD for the interaction with HNF1α. Moreover, we show that HNF4α cooperates with p300 to achieve the highest HNF1α‐mediated transcription rates. Our findings highlight a new way by which HNF4α can regulate gene expression and extend our knowledge of the complexity of the transcriptional network involving HNF4α and HNF1α.
Oxford University Press