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Differential regulation of major surface promoter in hepatitis B virus.

Abstract：

:The major surface promoter of human hepatitis B virus can produce three distinct groups of S transcripts. The initiation sites of these transcripts are in close proximity. Encompassing the ATG for the middle surface protein, the largest S transcript (+1) encodes the middle surface protein whereas the other two (+20 and +31) can only code for small surface protein. Sequence analysis does not reveal any TATA element. In this study, we employ deletion, linker scanning, and linker insertion analyses to study systematically the sequence requirements for the initiations of all three transcripts and their upstream regulatory sequences. Our study reveals that the sequence downstream of -16 is sufficient for precise initiation of all three groups of S transcripts. The 3' boundary of minimal promoter element is +15 for the +1 transcript, whereas it is +39 for both +20 and +31 transcripts. Furthermore, there are distinct sequence requirements for the initiations of three groups of S transcripts. The sequences from -17 to -10 and from -1 to +7 are required for the initiation of +1 transcript, the sequence from +16 to +39 is essential for the +20 transcript, and the sequences from -17 to -10 and from +24 to +39 are required for the + 31 transcript. Our results also suggest that the transcription initiations of major surface promoter may be mediated in part by initiators. The initiations of these three groups of S transcripts are under differential regulation. The region from -39 to -16 containing both negative and positive regulatory elements selectively regulates the transcription levels of the two major S transcripts. Most notably, mutation of the sequence from -17 to -10, which contains a Sp1 site, leads to an increase in the imprecise initiation at +1 site and depresses the initiation of +20 and, to a greater extent, +31 transcript. The relevance of differential regulation of major surface promoter to the varied production of different surface protein isoforms in viral life cycle is discussed.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Kuo YL,Ting LP

doi

10.1089/dna.1997.16.545

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

545-57

issue

eissn

1044-5498

issn

1557-7430

journal_volume

pub_type

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Differential regulation of major surface promoter in hepatitis B virus.