UTF1, A NOVEL TRANSCRIPTIONAL COACTIVATOR EXPRESSED IN PLURIPOTENT EMBRYONIC STEM-CELLS AND EXTRAEMBRYONIC CELLS

We have obtained a novel transcriptional cofactor, termed undifferenti ated embryonic cell transcription factor 1 (UTF1), from F9 embryonic c arcinoma (EC) cells. This protein is expressed in EC and embryonic ste m cells, as well as in germ line tissues, but could not be detected in any of the other adult mouse tissues tested. Furthermore, when EC cel ls are induced to differentiate, UTF1 expression is rapidly extinguish ed, In normal mouse embryos, UTF1 mRNA is present in the inner cell ma ss, the primitive ectoderm and the extra-embryonic tissues, During the primitive streak stage, the induction of mesodermal cells is accompan ied by the down-regulation of UTF1 in the primitive ectoderm, However, its expression is maintained for up to 13.5 days post-coitum in the e xtra-embryonic tissue. Functionally, UTF1 boosts the level of transcri ption of the adenovirus E2A promoter. However, unlike the pluripotent cell-specific E1A-like activity, which requires the E2F sites of the E 2A promoter for increased transcriptional activation, UTF1-mediated ac tivation is dependent on the upstream ATF site of this promoter. This result indicates that UTF1 is not a major component of the E1A-like ac tivity present in pluripotent embryonic cells. Further analyses reveal ed that UTF1 interacts not only with the activation domain of ATF-2, b ut also with the TFIID complex in vivo. Thus, UTF1 displays many of th e hallmark characteristics expected for a tissue-specific transcriptio nal coactivator that works in early embryogenesis.