Injury induces rapid changes in hepatocyte nuclear factor-1: DNA binding

Area of Science:

• Molecular biology
• Genetics
• Biochemistry

Background:

• Liver transcriptional regulation is key to the acute phase response.
• Molecular mechanisms of injury-induced gene transcription are not well understood.
• Hepatocyte nuclear factor (HNF)-1 is a liver-specific transcription factor involved in acute phase gene regulation.

Purpose of the Study:

• To investigate the effect of injury on HNF-1 binding activity in vivo.
• To explore the link between injury and transcriptional regulatory mechanisms.

Main Methods:

• Liver nuclear extracts were obtained from animals subjected to burn or sham burn injury.
• Electrophoretic mobility shift analysis was used to assess HNF-1 binding activity, affinity, and off-rate.

Main Results:

• HNF-1 binding activity decreased by 28% 1.5 hours post-injury.
• HNF-1 affinity for DNA significantly decreased (dissociation constant increased from 0.6 nm to 11.8 nm) due to an increased off-rate.

Conclusions:

• Burn injury markedly reduces HNF-1 binding activity in the liver.
• Decreased HNF-1 affinity for its DNA binding site is a key mechanism for this reduction.
• These findings reveal a novel mechanism for rapid modulation of acute phase gene transcription following injury.