Integrated hepatitis B virus DNA preserves the binding sequence of transcription factor Yin and Yang 1 at the virus-cell junction

Accumulated findings have indicated that hepatitis B virus (HBV) DNA integr ates into the cellular DNA of HBV-infected chronic hepatitis tissues. The i ntegrated sequence (IS) of HBV DNA at the virus-cell junction is conserved in a 25-bp region which is adjacent to direct repeat 1. A cellular protein which we purified from the nuclear extract of HepG2 cells binds to the IS a nd was designated IS binding protein 3 (ISBP3). The amino acid sequence of ISBP3 was determined and found to be identical to that of transcription ini tiation factor Yin and Yang 1 (YY1). An antibody against C-terminal amino a cids of YY1 recognized ISBP3 in a Western blot analysis and an electrophore tic mobility shift assay. Furthermore, ISBP3 also interacted with Y3, which corresponds to the YY1 binding sequence, to enhance intramolecular recombi nation of polyomavirus DNA. Although YY1 is known as a transcription factor , the IS did not exhibit any effect on the transcription of precore and pre genome RNAs. The possible involvement of YY1 in the intramolecular recombin ation of linear replicative HBV DNA has been examined CY. Hayashi et al,, u npublished data). Data suggest that WI is involved in the joining reaction between HBV DNA and cellular DNA to form the virus-cell junction.