Hepatocyte Nuclear Factor 4 enhances the Hepatocyte Nuclear Factor 1 -mediated activation of transcription
Year: 2004
Type: article
Abstract: 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.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkh581
Author: J. Eeckhoute
Institution: Inserm
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2007722784