Abstract
Nanog, a homeodomain (HD) transcription factor, plays a critical role in the maintenance of embryonic stem (ES) cell self-renewal. Here, we report the identification of an alternatively-spliced variant of nanog. This variant lacked a stretch of amino acids (residues 168-183) located between the HD and tryptophan-repeat (WR) of the previously-reported full length sequence, suggesting that the deleted sequence functions as a linker and possibly affects the flexibility of the C-terminal transactivation domain relative to the DNA binding domain. Expression of mRNA encoding the splice variant, designated as nanog-delta 48, was much lower than that of the full length version in human ES cells. The ratio of nanog-delta 48 transcript to full length transcript increased, however, in multipotent adult progenitor cells. EMSA analysis revealed that both forms of Nanog were able to bind a nanog binding sequence with roughly the same affinity. A reporter plasmid assay also showed that both variants of nanog modestly repressed transactivation of gata-4, whose expression is proposed to be inhibited by nanog, with comparable potency. We conclude that, despite the difference in primary structure and expression pattern in various stem cells, the alternatively-spliced variant of Nanog has similar activity to that of the full length version.
Original language | English (US) |
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Pages (from-to) | 601-607 |
Number of pages | 7 |
Journal | Experimental and Molecular Medicine |
Volume | 37 |
Issue number | 6 |
DOIs | |
State | Published - Dec 31 2005 |
Externally published | Yes |
Keywords
- Alternative splicing
- GATA4 transcription factor
- Hematopoietic stem cells
- NANOG protein human
- Totipotent stem cells
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry