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Publication : Tpt1 activates transcription of oct4 and nanog in transplanted somatic nuclei.

First Author  Koziol MJ Year  2007
Journal  Curr Biol Volume  17
Issue  9 Pages  801-7
PubMed ID  17442571 Mgi Jnum  J:121860
Mgi Id  MGI:3712410 Doi  10.1016/j.cub.2007.03.062
Citation  Koziol MJ, et al. (2007) Tpt1 activates transcription of oct4 and nanog in transplanted somatic nuclei. Curr Biol 17(9):801-7
abstractText  Nuclear transfer to eggs or oocytes provides a potential route for cell-replacement therapies because oocytes directly reprogram transplanted mammalian somatic-cell nuclei such that they have an embryo-like pattern of gene expression. This includes a large increase in the mRNA level of the stem-cell marker gene oct4. We have developed a novel procedure to identify new proteins that greatly increase the level of oct4 mRNA upon nuclear transfer. We have isolated Xenopus oocyte proteins that bind to the regulatory region of the mouse oct4 gene and identified these by mass spectrometry. The proteins include the retinoic-acid-receptor gamma, a known repressor of oct4 transcription, and Tpt1, a cancer-associated factor. The depletion of transcripts of retinoic-acid receptor gamma from oocytes increases oct4 and nanog transcription as expected, and depletion of tpt1 transcripts in oocytes reduces oct4 and nanog transcription in injected HeLa nuclei. An elevation of tpt1 transcripts in oocytes results in an earlier activation of oct4 transcription. Therefore, we identify a novel role for tpt1 in activating pluripotency genes upon nuclear transfer. Our results help to elucidate the mechanism by which somatic-cell nuclei are reprogrammed to have an embryo-like pattern of gene expression.
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