Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage
Rajini Srinivasan, Nataliya Nady, Neha Arora, Laura J Hsieh, Tomek Swigut, Geeta J. Narlikar, Mark Wossidlo, Joanna Wysocka
Abstract
microsatellites, repeat sequences prone to genomic instability. Zscan4-associated microsatellite regions are characterized by low nuclease sensitivity and high histone occupancy. In vitro, Zscan4 binds nucleosomes and protects them from disassembly upon torsional strain. Furthermore, Zscan4 depletion leads to elevated DNA damage in 2C mouse embryos in a transcription-dependent manner. Together, our results identify Zscan4 as a DNA sequence-dependent microsatellite binding factor and suggest a developmentally regulated mechanism, which protects fragile genomic regions from DNA damage at a time of embryogenesis associated with high transcriptional burden and genomic stress.