B κ NFin the Mouse Liver: Involvement of Cytomegalovirus Major Immediate-Early Reactivation of the Previously Silenced

The cytomegalovirus (CMV) major immediate-early promoter/enhancer is active in many cell culture sys-tems and is considered to be one of the strongest promoters in vitro. However, when this promoter was usedin in vivo approaches to gene therapy, it was silenced within a few weeks in several organs including the liver.In this study, we demonstrated transcriptional inactivation of the CMV promoter in mouse liver. In contrastto the CMV promoter, a hybrid promoter consisting of a minimal CMV promoter and the enhancer II ofhepatitis B virus was active for at least 11 weeks in mouse liver. While investigating the reason for the shutdownof the CMV promoter, we did not find evidence for methylation of adenovirus DNA in the region of transgeneinsertion, but we could show that the silenced CMV promoter was reactivated after lipopolysaccharidetreatment of mice or partial hepatectomy. Both stimuli are known to activate the transcription factor NF