Phenotypic Complementation Establishes Requirements for Specific POU Domain and Generic Transactivation Function of Oct-3/4 in Embryonic Stem Cells

Laboratory for Pluripotent Stem Cell Studies, RIKEN, Вако, Saitama, Japan
Molecular and Cellular Biology (Impact Factor: 4.78). 04/2002; 22(5):1526-36. DOI: 10.1128/MCB.22.5.1526-1536.2002
Source: PubMed


Transcription factors of the POU family govern cell fate through combinatorial interactions with coactivators and corepressors.
The POU factor Oct-3/4 can define differentiation, dedifferentation, or self-renewal of pluripotent embryonic stem (ES) cells
in a sensitive, dose-dependent manner (H. Niwa, J.-I. Miyazali, and A. G. Smith, Nat. Genet. 24:372-376, 2000). Here we have
developed a complementation assay based on the ability of Oct-3/4 transgenes to rescue self-renewal in conditionally null
ES cells and used this to define which domains of Oct-3/4 are required to sustain the undifferentiated stem cell phenotype.
Surprisingly, we found that molecules lacking either the N-terminal or C-terminal transactivation domain, though not both,
can effectively replace full-length Oct-3/4. Furthermore, a fusion of the heterologous transactivation domain of Oct-2 to
the Oct-3/4 POU domain can also sustain self-renewal. Thus, the unique function of Oct-3/4 in ES cell propagation resides
in combination of the specific POU domain with a generic proline-rich transactivation domain. Interestingly, however, Oct-3/4
target gene expression elicited by the N- and C-terminal transactivation domains is not identical, indicating that at least
one class of genes activated by Oct-3/4 is not required for ES cell propagation.

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Available from: Jun-ichi Miyazaki, Jan 10, 2014
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