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Journal of Virology, October 2004, p. 10856-10864, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10856-10864.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Nuclear Respiratory Factor 1 Plays an Essential Role in Transcriptional Initiation from the Hepatitis B Virus X Gene Promoter

Yumiko Tokusumi,1 Sharleen Zhou,2 and Shinako Takada1*

Department of Biochemistry and Molecular Biology, Genes and Development Program of the Graduate School of Biomedical Sciences, University of Texas M. D. Anderson Cancer Center, Houston, Texas,1 Howard Hughes Medical Institute, University of California, Berkeley, California2

Received 17 February 2004/ Accepted 2 June 2004

The X gene of hepatitis B virus (HBV) is one of the major factors in HBV-induced hepatocarcinogenesis and is essential for the establishment of productive HBV replication in vivo. Recent studies have shown that the X gene product targets mitochondria and induces calcium flux, thereby activating Ca+-dependent signal transduction pathways. However, regulatory mechanisms of X gene expression have remained unclear. Previous studies had localized a minimal promoter activity to a 21-bp GC-rich sequence located 130 bp upstream of the X protein coding region and showed that there was a cellular protein bound to this DNA. Interestingly, the 21-bp sequence identified as an X gene minimal promoter does not contain any previously identified core promoter elements, such as a TATA box. To better understand the mechanisms of transcriptional initiation of the X gene, we set out to biochemically purify the binding protein(s) for the 21-bp DNA. We report here the identification of the X gene minimal promoter-binding activity as nuclear respiratory factor 1 (NRF1), a previously known transcription factor that activates the majority of nucleus-encoded mitochondrial genes and various housekeeping genes. Primer extension analyses of the X mRNAs show that mutations at the binding site specifically inactivate transcription from this promoter and that a dominant-negative NRF1 mutant and short interfering RNAs inhibit transcription from this promoter. Therefore, NRF1 specifically binds the 21-bp minimal promoter and positively contributes to transcription of the X gene. Simultaneous activation of the X gene and mitochondrial genes by NRF1 may allow the X protein to target mitochondria most efficiently.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Box 117, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 745-1307. Fax: (713) 563-2968. E-mail: stakada{at}mdanderson.org.

Journal of Virology, October 2004, p. 10856-10864, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10856-10864.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hossain, M. B., Ji, P., Anish, R., Jacobson, R. H., Takada, S. (2009). Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1) and Plays a Role in NRF-1 Transcriptional Regulation. J. Biol. Chem. 284: 8621-8632 [Abstract] [Full Text]  
  • Tokusumi, Y., Ma, Y., Song, X., Jacobson, R. H., Takada, S. (2007). The New Core Promoter Element XCPE1 (X Core Promoter Element 1) Directs Activator-, Mediator-, and TATA-Binding Protein-Dependent but TFIID-Independent RNA Polymerase II Transcription from TATA-Less Promoters. Mol. Cell. Biol. 27: 1844-1858 [Abstract] [Full Text]  
  • Bhattacharya, S., Takada, S., Jacobson, R. H. (2007). Structural analysis and dimerization potential of the human TAF5 subunit of TFIID. Proc. Natl. Acad. Sci. USA 104: 1189-1194 [Abstract] [Full Text]  


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