Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA Box.

We have recently isolated a novel transcriptional coactivator, UTF1, which is expressed mainly in pluripotent embryonic stem cells (Okuda, A., Fukushima, A., Nishimoto, M., Orimo, A., Yamagishi, T., Nabeshima, Y., Kuro-o, M., Nabeshima, Y., Boon, K., Keaveney, M., Stunnenberg, H. G., and Muramatsu, M. EMBO J. 17, 2019-2032, 1998). The UTF1 does not activate transcription nonspecifically, but boosts the level of transcription strictly in a specific upstream factor, ATF-2, dependent manner in mammalian cells. However, when expressed in yeast cells, the UTF1 displays a distinct activity, being able to augment the activity of minimal promoter bearing only the TATA element. Thus, these results indicate that certain domains of UTF1 render the factor inactive in terms of stimulating transcription through the basal transcription machinery in the absence of promoter-bound ATF-2 in mammalian cells. Here we report that the region bearing the leucine zipper motif is responsible for such biochemical properties of the UTF1. Indeed, UTF1 lacking functional leucine zipper is able to rather promiscuously stimulate transcription from a number of basal gene promoters such as those of hsp70 and E1B genes in mammalian cells. We have also shown that this activation is executed through TATA box by the experiments using a TBP allele with an altered TATA-binding specificity. Moreover, we have found that Dr1-mediated repression of transcription can be overcome by expression of this mutant UTF1, indicating that the observed stimulation of transcription is at least in part due to its action as an anti-repressor. Copyright 1999 Academic Press.