Injury induces rapid changes in hepatocyte nuclear factor-1: DNA binding.
BACKGROUND
Transcriptional regulation in the liver plays a critical role in mediating the acute phase response to injury. The molecular mechanisms driving these transcriptional events, however, are poorly defined in vivo. The liver-specific transcription factor hepatocyte nuclear factor (HNF)-1 binds to the 5' upstream region of many acute phase genes. To explore the connection between injury and transcriptional regulatory mechanisms, we investigated the effect of injury on HNF-1 binding activity.


METHODS
Liver nuclear extracts were prepared from animals after burn or anesthetized sham burn injury. HNF-1 binding activity, affinity, and off rate were assessed by electrophoretic mobility shift analysis.


RESULTS
HNF-1 binding activity decreased by 28% 1 1/2 hours after injury. The dissociation constant for HNF-1 increased from 0.6 nm to 11.8 nm at 1 1/2 hours after burn injury partly because of an increase in off rate for the HNF-1: DNA complex.


CONCLUSIONS
Burn injury leads to a significant decrease in HNF-1 binding activity as a result of decreased affinity of HNF-1 for DNA. These injury-induced alterations in binding of a liver-specific transcription factor for its DNA binding site represent a mechanism for rapidly modulating acute phase gene transcription in vivo.
Burke
P A
PA
Department of Surgery, Deacones Hospital/Harvard Medical School, Boston, Mass, USA.
Luo
M
M
Zhu
J
J
Yaffe
M B
MB
Forse
R A
RA
D000818:Animals; D001483:Base Sequence; D002056:Burns / Q000503:physiopathology*; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D004586:Electrophoresis; D005260:Female; D008099:Liver / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human