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Nucleic Acids Research, 1994, Vol. 22, No. 13 2453-2459
© 1994


MOLECULAR BIOLOGY

The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in nonpermissive cells

Ru Liu, Joan Baillie, J.G. Patrick Sissons and John H. Sinclair*

Department of Medicine, University of Cambridge Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK

*To whom correspondence should be addressed

Received May 11, 1994. Revised June 10, 1994. Accepted June 10, 1994.

We have previously shown that repression of human cytomegalovirus (HCMV) major immediate early (IE) gene expression in non-permissive human teratocarcinoma (T2) cells is associated with a number of nuclear factors which bind to the imperfect dyad symmetry located in the modulator region upstream of the major IE enhancer as well as to the 21 bp repeat elements within the enhancer. Differentiation of T2 cells with retinoic acid (RA) results in a decrease in binding of some of these nuclear factors to these sites and deletion of these specific binding sites from major IE promoter/reporter constructs results in increased IE promoter activity in normally non-permissive cells. In this study, we demonstrate that the transcription factor YY1, which can negatively regulate the adenoassociated virus P5 promoter, directly binds to both the imperfect dyad symmetry and the 21 bp repeat elements in the HCMV major IE promoter/regulatory region and mediates repression of HCMV IE gene expression. This strongly suggests that YY1 plays an important role in regulating HCMV expression in nonpermissive cells.


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