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Nucleic Acids Research, 1992, Vol. 20, No. 7 1669-1674
© 1992

MOLECULAR BIOLOGY

Transformation of a novel direct-repeat repressor element into a promoter and enhancer by multimerisation

Kin-Chow Chang, Ekkehard Hansen, Thomas Jaenicke, Geoffrey Goldspink and Peter Butterworth

Unit of Veterinary Molecular and Cellular Biology, The Royal Veterinary College, University of London Royal College Street, London NW1 OTU 1University of Surrey, Guildford Surrey GU2 5X, UK

Received December 16, 1991. Revised February 25, 1992. Accepted February 25, 1992.

Studies on the regulation of interferon (IFN) responsive genes have mainly been centred on the highly conserved IFN stimulated responsive elements (ISREs) which can mediate type I and II IFN inducibility. To date little is known about other functional cis-acting regulatory motifs in IFN responsive genes. We report here on the identification of a repressor element in the human MxA gene defined to a 19 base pair (bp) region which houses a 9 bp direct repeat. DNA-speciflc protein binding on this element is not affected by IFN treatment and is distinct from ISRE binding proteins. Remarkably, contrary to expectations, when the repressor element is multimerised and spliced, in either orientation, to a reporter gene it behaves like a functional, constitutive promoter. Positioning the multimerised element in front of the SV40 enhanceriess promoter also led to enhanced expression. The same protein(s) seem to bind to both the single repressor element and its multimerised form. This discovery of phenotypic reversal on a repressor element via muitimerisation may have important implications in vivo.


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