UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells

Akihiko Okuda, Akiko Fukushima, Masazumi Nishimoto, Akira Orimo, Toshiyuki Yamagishi, Yoko Nabeshima, Makoto Kuro-o, Yo Ichi Nabeshima, Kathy Boon, Marie Keaveney, Hendrik G. Stunnenberg, Masami Muramatsu

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

We have obtained a novel transcriptional cofactor, termed undifferentiated embryonic cell transcription factor 1 (UTF1), from F9 embryonic carcinoma (EC) cells. This protein is expressed in EC and embryonic stem 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 cells are induced to differentiate, UTF1 expression is rapidly extinguished. In normal mouse embryos, UTF1 mRNA is present in the inner cell mass, the primitive ectoderm and the extra-embryonic tissues. During the primitive streak stage, the induction of mesodermal cells is accompanied 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 extra-embryonic tissue. Functionally, UTF1 boosts the level of transcription of the adenovirus E2A promoter. 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. This result indicates that UTF1 is not a major component of the E1A-like activity present in pluripotent embryonic cells. Further analyses revealed that UTF1 interacts not only with the activation domain of ATF-2, but also with the TFIID complex in vivo. Thus, UTF1 displays many of the hallmark characteristics expected for a tissue-specific transcriptional coactivator that works in early embryogenesis.

Original languageEnglish (US)
Pages (from-to)2019-2032
Number of pages14
JournalEMBO Journal
Volume17
Issue number7
DOIs
StatePublished - Apr 1 1998

Fingerprint

Pluripotent Stem Cells
Embryonic Stem Cells
Stem cells
Transcription Factors
Tissue
Chemical activation
Ectoderm
Cells
Transcription Factor TFIID
Carcinoma
Transcription
Primitive Streak
Messenger RNA
Adenoviridae
Germ Cells

Keywords

  • ATF-2
  • E1A-like activity
  • Embryonic stem cells
  • Transcriptional coactivator

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Okuda, A., Fukushima, A., Nishimoto, M., Orimo, A., Yamagishi, T., Nabeshima, Y., ... Muramatsu, M. (1998). UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. EMBO Journal, 17(7), 2019-2032. https://doi.org/10.1093/emboj/17.7.2019

UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. / Okuda, Akihiko; Fukushima, Akiko; Nishimoto, Masazumi; Orimo, Akira; Yamagishi, Toshiyuki; Nabeshima, Yoko; Kuro-o, Makoto; Nabeshima, Yo Ichi; Boon, Kathy; Keaveney, Marie; Stunnenberg, Hendrik G.; Muramatsu, Masami.

In: EMBO Journal, Vol. 17, No. 7, 01.04.1998, p. 2019-2032.

Research output: Contribution to journalArticle

Okuda, A, Fukushima, A, Nishimoto, M, Orimo, A, Yamagishi, T, Nabeshima, Y, Kuro-o, M, Nabeshima, YI, Boon, K, Keaveney, M, Stunnenberg, HG & Muramatsu, M 1998, 'UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells', EMBO Journal, vol. 17, no. 7, pp. 2019-2032. https://doi.org/10.1093/emboj/17.7.2019
Okuda, Akihiko ; Fukushima, Akiko ; Nishimoto, Masazumi ; Orimo, Akira ; Yamagishi, Toshiyuki ; Nabeshima, Yoko ; Kuro-o, Makoto ; Nabeshima, Yo Ichi ; Boon, Kathy ; Keaveney, Marie ; Stunnenberg, Hendrik G. ; Muramatsu, Masami. / UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. In: EMBO Journal. 1998 ; Vol. 17, No. 7. pp. 2019-2032.
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abstract = "We have obtained a novel transcriptional cofactor, termed undifferentiated embryonic cell transcription factor 1 (UTF1), from F9 embryonic carcinoma (EC) cells. This protein is expressed in EC and embryonic stem 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 cells are induced to differentiate, UTF1 expression is rapidly extinguished. In normal mouse embryos, UTF1 mRNA is present in the inner cell mass, the primitive ectoderm and the extra-embryonic tissues. During the primitive streak stage, the induction of mesodermal cells is accompanied 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 extra-embryonic tissue. Functionally, UTF1 boosts the level of transcription of the adenovirus E2A promoter. 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. This result indicates that UTF1 is not a major component of the E1A-like activity present in pluripotent embryonic cells. Further analyses revealed that UTF1 interacts not only with the activation domain of ATF-2, but also with the TFIID complex in vivo. Thus, UTF1 displays many of the hallmark characteristics expected for a tissue-specific transcriptional coactivator that works in early embryogenesis.",
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