Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog

Sun Kim Jung, Jiha Kim, Soo Kim Byung, Yong Chung Hee, Yiul Lee Young, Choon Sik Park, Seek Lee Young, Han Lee Young, Yup Chung Il

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 languageEnglish (US)
Pages (from-to)601-607
Number of pages7
JournalExperimental and Molecular Medicine
Volume37
Issue number6
DOIs
StatePublished - Dec 31 2005
Externally publishedYes

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

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