The gene for the embryonic stem cell coactivator UTF1 carries a regulatoryelement which selectively interacts with a complex composed of Oct-3/4 andSox-2

UTF1 is a transcriptional coactivator which has recently been isolated and found to be expressed mainly in pluripotent embryonic stem (ES) cells (A. O kuda, A. Fukushima, M. Nishimoto, et at, EMBO J. 17:2019-2032, 1998). To ga in insight into the regulatory network of gene expression in ES cells, we h ave characterized the regulatory elements governing UTF1 gene expression. T he results indicate that the UTF1 gene is one of the target genes of an emb ryonic octamer binding transcription factor, Oct-3/4. UTF1 expression is, l ike the FGF-4 gene, regulated by the synergistic action of Oct-314 and anot her embryonic factor, Sox-2, implying that the requirement for Sox-2 by Oct -3/4 is not limited to the FGF-4 enhancer but is rather a general mechanism of activation for Oct-3/4. Our biochemical analyses, however, also reveal one distinct difference between these two regulatory elements: unlike the F GF-4 enhancer, the UTF1 regulatory element can, by its one-base difference from the canonical octamer-binding sequence, selectively recruit the comple x comprising Oct-314 and Sox-2 and preclude the binding of the transcriptio nally inactive complex containing Oct-1 or Oct-6. Furthermore, our analyses reveal that these properties are dictated by the unique ability of the Oct -314 POU-homeodomain that recognizes a variant of the Octamer motif in the UTF1 regulatory element.