| Research Abstract |
STAT3 is a transcriptional factor that is involved in self-renewal of embryonic stem (ES) cells. To identify target genes of STAT3 in the self-renewal, we searched for a gene(s) that shows higher expression in undifferentiated ES cells than in differentiated ES cells by using subtraction method and DNA microarray, and found several candidate genes. Of them, we focused our attention on the following two genes.
1. zinc-finger protein (zfp) 57 Oct-3/4, a pluripotent stem cell-specific transcription factor, plays a critical role in the self-renewal of ES cells. Several evidences suggest that gene expression via Oct-3/4 requires an unidentified co-factor(s). We found that Zfp57 is expressed during the self-renewal of ES cells, while its expression is reduced upon differentiation. By co-immunoprecipitation assay, it was also found that Zfp57 interacts with Oct-3/4. Furthermore, Zfp57 enhanced the transcriptional activity of Oct-3/4 towards the promoter of rex-1, an Oct-3/4 target gene, in hum
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an embryonic kidney 293 cells. Our data suggest that Zfp57, a target of STAT3, is one of the Oct-3/4 co-factors, and raise the possibility that this protein may cooperate with Oct-3/4 in induction of Rex-1, which in turn may play an important role in the self-renewal of ES cells.
2. Embryonic ectoderm development (eed) Recent studies revealed that gene expression is tightly associated with acetylation of histone, which is controlled by histone acetyltransferases and histpne deacylases (HDACs). Bed, a member of the polycomb family, is known to bind with HDAC. We found that Bed is one of the downstream molecules of STATS. Treatment of ES cells with trichostatin A, an HDAC inhibitor, led to the initiation of differentiation, suggesting that histone acetylation is involved in regulation of the self-renewal. Interestingly, we found that Bed forms a complex also with Rex-1. Since deacylation ofhistone generally results in repression of gene expression, these results suggest the possibility that the Eed・Rex-1・HDAC complex may maintain the undifferentiated state of ES cells by suppressing the expression of a differentiation-inducing gene(s). Less
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