Negative regulation of a heterologous promoter by human cytomegalovirus immediate-early protein IE2.

Abstract:

:The HCMV IE2 protein promiscuously activates transcription of many viral and cellular genes. IE2 also negatively autoregulates its own expression by binding to a strategically positioned IE2 binding site, called CRS, located immediately downstream of the TATA box of the HCMV major IE promoter. Here we show that IE2 is able to repress transcription driven by a heterologous promoter, RSV LTR. Repression of RSV LTR by IE2 is completely dependent of DNA sequences downstream of the TATA box of RSV LTR. A DNA sequence, 5'-CGATACAATAAACG-3', evidently matching the proposed CRS consensus sequence, is located between nucleotides -13 and +1 (relative to the transcription start site) of RSV LTR. Three lines of evidence support the notion that this RSV CRS element is involved in the IE2-mediated repression of RSV LTR. First, introduction of mutation to the RSV CRS element renders to the mutant RSV LTR resistance to IE2-mediated repression. Second, a mutant IE2 defective in DNA binding cannot downregulate transcription from RSV LTR. Third, IE2 specifically binds to the wild-type, but not the mutant, RSV CRS element in vitro. These data, in conjunction with previous works, demonstrate that IE2 can passively repress transcription of homologous and heterologous promoters that contain a CRS element.

journal_name

Virology

journal_title

Virology

authors

Tsai HL,Kou GH,Tang FM,Wu CW,Lin YS

doi

10.1006/viro.1997.8855

subject

Has Abstract

pub_date

1997-11-24 00:00:00

pages

372-9

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(97)98855-3

journal_volume

238

pub_type

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