DIFFERENTIAL EXPRESSION OF THE HUMAN ST5 GENE IN HELA-FIBROBLAST HYBRID CELL-LINES MEDIATED BY YY1 EVIDENCE THAT YY1 - PLAYS A PART IN TUMOR SUPPRESSION

Through a mutational analysis of a differentially regulated enhancer, we present evidence that supports a role for the transcription factor YY1 in tumor suppression in HeLa/fibroblast somatic cell hybrids, The human ST5 gene was previously shown to be expressed as three RNA speci es, 4.6, 3.1 and 2.8 kb in length, Whereas the two larger species are expressed at similar levels in all cell lines examined, the 2.8 kb mRN A is expressed specifically in non-tumorigenic hybrids, In this study, the basis for the differential expression of this mRNA species was in vestigated, The message was shown to originate from a promoter located within an intron of the ST5 gene, An enhancer located similar to 1500 nt upstream of the start site was required for cell type specific exp ression, Mutational analysis of this enhancer revealed an AP1 site and five YY1 sites which were necessary for full enhancer activity, Level s of YY1 DNA binding activity were found to be as much as 6-fold highe r in the non-tumorigenic cells relative to the tumorigenic cells, whil e AP1 activity was similar in both cell types, These results suggest t hat a signaling pathway targeting YY1 may play an important role in tu mor suppression in HeLa-fibroblast hybrids.