This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doitsh, G. Articles by Shaul, Y. Search for Related Content PubMed PubMed Citation Articles by Doitsh, G. Articles by Shaul, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2004, p. 1799-1808, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1799-1808.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Enhancer I Predominance in Hepatitis B Virus Gene Expression

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel

Received 29 July 2003/ Returned for modification 9 September 2003/ Accepted 11 November 2003

Previous studies of human hepatitis B virus (HBV) transcription revealed the requirement of two enhancer elements. Enhancer I (EnhI) is located upstream of the X promoter and is targeted by multiple activators, including basic leucine zipper proteins, and enhancer II (EnhII) is located upstream to the PreCore promoter and is targeted mainly by nuclear receptors (NRs). The mode of interplay between these enhancers and their unique contributions in regulating HBV transcription remained obscure. By using time course analysis we revealed that the HBV transcripts are categorized into early and late groups. Chang (CCL-13) cells are impaired in expression of the late transcripts. This could be corrected by overexpressing EnhII activators, such as hepatocyte nuclear factor 4, the retinoid X receptor , and the peroxisome proliferator-activated receptor , suggesting that in Chang cells EnhI but not EnhII is active. Replacing the 5'-end EnhI sequence with a synthetic Gal4 response (UAS) DNA fragment ceased the production of the early transcripts. Under this condition NR overexpression poorly activated EnhII. However, activation of the UAS by Gal4-p53 restored both the expression of the early transcripts and the EnhII response to NRs. Thus, a functional EnhI is required for activation of EnhII. We found a major difference between Gal4-p53 and Gal4-VP16 behavior. Gal4-p53 activated the early transcripts, while Gal4-VP16 inhibited the early transcripts but activated the late transcripts. These findings indicate that the composition of the EnhI binding proteins may play a role in early to late switching. Our data provides strong evidence for the role of EnhI in regulating global and temporal HBV gene expression.

This article has been cited by other articles:

• Shlomai, A., Paran, N., Shaul, Y. (2006). PGC-1{alpha} controls hepatitis B virus through nutritional signals. Proc. Natl. Acad. Sci. USA 103: 16003-16008 [Abstract] [Full Text]