Transcriptional stimulation by hepatocyte nuclear factor-6. Target-specific recruitment of either CREB-binding protein (CBP) or p300/CBP-associated factor (p/CAF).
Transcription factors of the ONECUT class, whose prototype is HNF-6, contain a single cut domain and a divergent homeodomain characterized by a phenylalanine at position 48 and a methionine at position 50. The cut domain is required for DNA binding. The homeodomain is required either for DNA binding or for transcriptional stimulation, depending on the target gene. Transcriptional stimulation by the homeodomain involves the F48M50 dyad. We investigate here how HNF-6 stimulates transcription. We identify transcriptionally active domains of HNF-6 that are conserved among members of the ONECUT class and show that the cut domain of HNF-6 participates to DNA binding and, via a LXXLL motif, to transcriptional stimulation. We also demonstrate that, on a target gene to which HNF-6 binds without requirement for the homeodomain, transcriptional stimulation involves an interaction of HNF-6 with the coactivator CREB-binding protein (CBP). This interaction depends both on the LXXLL motif of the cut domain and on the F48M50 dyad of the homeodomain. On a target gene for which the homeodomain is required for DNA binding, but not for transcriptional stimulation, HNF-6 interacts with the coactivator p300/CBP-associated factor but not with CBP. These data show that a transcription factor can act via different, sequence-specific, mechanisms that combine distinct modes of DNA binding with the use of different coactivators.
Lannoy
V J
VJ
Hormone and Metabolic Research Unit, Université catholique de Louvain and Christian de Duve Institute of Cellular Pathology (ICP), Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Rodolosse
A
A
Pierreux
C E
CE
Rousseau
G G
GG
Lemaigre
F P
FP
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018390:Gene Targeting; D051559:Hepatocyte Nuclear Factor 6; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051559:Hepatocyte Nuclear Factor 6; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C496607:Onecut1 protein, rat; C494365:Crebbp protein, rat