HUMAN ZFM1 PROTEIN IS A TRANSCRIPTIONAL REPRESSOR THAT INTERACTS WITHTHE TRANSCRIPTION ACTIVATION DOMAIN OF STAGE-SPECIFIC ACTIVATOR PROTEIN

Stage specific activator protein (SSAP) is the transcription factor re sponsible for the activation of the sea urchin late H1 gene at the mid -blastula stage of embryogenesis. SSAP contains an extremely potent tr anscription activation domain that functions 4-5-fold better than VP16 in a variety of mammalian cell lines. We used the two-hybrid screenin g technique to identify human cDNAs from an HL60 cell-derived cDNA lib rary that encode proteins that interact with the transcription activat ion domain of SSAP. One of these cDNAs encodes ZFM1, a protein previou sly identified at the locus linked to multiple endocrine neoplasia typ e 1 (MEN1) and as presplicing factor SF1. Functional assays establish the ZFM1 protein as a transcriptional repressor. ZFM1 protein represse s Gal4-GQC-mediated transcription, and this activity requires both a r epression domain found in the N-terminal 137 amino acids of the protei n, as well as a GQC interaction region. The physiological significance of repression mediated by ZFM1 comes from the ability of its specific repression domain to function when fused to Gal4 and tethered to prom oters containing Gal4 binding sites. The activity is unique in that ac tivated but not basal transcription levels are affected.