Disease relevance of UTF1

• We have recently cloned a cDNA encoding an embryonic stem cell transcriptional coactivator termed UTF1 from the mouse F9 teratocarcinoma cell line (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. (1998) EMBO J. 17, 2019-2032) [1].
• Functionally, UTF1 boosts the level of transcription of the adenovirus E2A promoter [2].
• Moreover, UTF1 was also observed to have an effect on teratoma formation [3].

High impact information on UTF1

• Further analyses revealed that UTF1 interacts not only with the activation domain of ATF-2, but also with the TFIID complex in vivo [2].
• UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells [2].
• In normal mouse embryos, UTF1 mRNA is present in the inner cell mass, the primitive ectoderm and the extra-embryonic tissues [2].
• During the primitive streak stage, the induction of mesodermal cells is accompanied by the down-regulation of UTF1 in the primitive ectoderm [2].
• Thus, UTF1 displays many of the hallmark characteristics expected for a tissue-specific transcriptional coactivator that works in early embryogenesis [2].

Biological context of UTF1

• Chromosomal mapping analyses locate the gene at 7F5, the syntenic region of the human chromosome (10q26) where the human UTF1 gene is located [4].
• Here, we have isolated a genomic DNA fragment carrying the UTF1 gene and found that the gene contains two exons interrupted by a short intron [4].
• However, unlike the pluripotent cell-specific E1A-like activity, which requires the E2F sites of the E2A promoter for increased transcriptional activation, UTF1-mediated activation is dependent on the upstream ATF site of this promoter [2].
• Here, we demonstrate using Oct-3/4-Oct-6 chimeras that there is a precise correlation between the ability of proteins to form a complex on the UTF1 enhancer with Sox-2 and the ability to maintain the stem cell state in ES cells [3].
• To gain insight into the regulatory network of gene expression in ES cells, we have characterized the regulatory elements governing UTF1 gene expression [5].

Regulatory relationships of UTF1

• 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 [6].

Other interactions of UTF1

• Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity [1].
• Here we have cloned a cDNA for human UTF1 and identified two highly conserved domains termed conserved domain (CD)1 and CD2 [1].
• Moreover, in contrast to an earlier prediction based on in vitro binding studies, we demonstrate that the function of the HMG/POU cassettes of the FGF-4 and UTF1 genes does not differ significantly in these EC cell lines when tested in the context of a natural enhancer [7].
• 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 [6].
• Here we report that the region bearing the leucine zipper motif is responsible for such biochemical properties of the UTF1 [6].

References