Zscan4 Is Activated after Telomere Shortening in Mouse Embryonic Stem Cells

Stem Cell Reports. 2016 Apr 12;6(4):483-495. doi: 10.1016/j.stemcr.2016.02.010. Epub 2016 Mar 17.

Abstract

ZSCAN4 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Situ Hybridization, Fluorescence
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Models, Genetic
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Shortening / genetics*
  • Time Factors
  • Time-Lapse Imaging / methods
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Rex-1 protein, mouse
  • Transcription Factors
  • Zscan4c protein, mouse
  • Zscan4d protein, mouse
  • Green Fluorescent Proteins
  • Luciferases