Abstract
SummaryZSCAN4 is a DNA-binding protein that functions for telomere elongation and genomic stability. In vivo, it is specifically expressed at the two-cell stage during mouse development. In vitro, it is transiently expressed in mouse embryonic stem cells (ESCs), only in 5% of the population at one time. Here we attempted to elucidate when, under what circumstances, Zscan4 is activated in ESCs. Using live cell imaging, we monitored the activity of Zscan4 together with the pluripotency marker Rex1. The lengths of the cell cycles in ESCs were diverse. Longer cell cycles were accompanied by shorter telomeres and higher activation of Zscan4. Since activation of Zscan4 is involved in telomere elongation, we speculate that the extended cell cycles accompanied by Zscan4 activation reflect the time for telomere recovery. Rex1 and Zscan4 did not show any correlation. Taken together, we propose that Zscan4 is activated to recover shortened telomeres during extended cell cycles, irrespective of the pluripotent status.
Highlights
Zinc finger and SCAN domain containing 4 (ZSCAN4) is a DNA-binding protein that is expressed in two-cell stage embryos during mouse development (Falco et al, 2007)
It is transiently expressed in mouse embryonic stem cells (ESCs), only in 5% of the population at one time
Since activation of Zscan4 is involved in telomere elongation, we speculate that the extended cell cycles accompanied by Zscan4 activation reflect the time for telomere recovery
Summary
Zinc finger and SCAN domain containing 4 (ZSCAN4) is a DNA-binding protein that is expressed in two-cell stage embryos during mouse development (Falco et al, 2007). Zscan is transiently expressed in a minor population of embryonic stem cells (ESCs) at one time (Carter et al, 2008) but is eventually expressed in all (Zalzman et al, 2010). It functions for telomere elongation and genomic stability (Zalzman et al, 2010) and is considered as a rejuvenation factor. Among the pluripotency-associated genes, Oct3/4 ( known as Pou5f1), whose expression does not fluctuate, is an exception. We consider the promoter activity of Rex, which is high only when the expression of Oct3/4 is maintained at an optimal range, as a good indicator of pluripotency
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