Zscan4 mediates transient remodeling and transcriptional burst of heterochromatin in mouse embryonic stem cells

This SuperSeries is composed of the SubSeries listed below. Repetitive sequences such as telomeres, centromeres, and retrotransposons are packed in permanently-condensed and transcriptionally-silenced heterochromatin, whose maintenance is critical for the genome stability. We have recently found that mouse ES cells occasionally go through a unique cell state marked by the transient expression of Zscan4, which plays a key role in long-term genome stability. Here we report our unexpected and counterintuitive finding that the Zscan4+ state is accompanied by a Zscan4-mediated rapid activation and repression of heterochromatin: the burst of transcription from heterochromatin coincided with its transient histone hyperacetylation and DNA demethylation, the clustering of pericentromeric heterochromatin in the perinucleolar region, and the accumulation of chromatin remodeling complexes for both activation (HATs, SWI/SNF) and repression (HDACs, LSD1/KDM1A, NuRD) on heterochromatin. Overall, these findings suggest that ES cells maintain their extraordinary genome stability and immortality by transiently taking extreme measures – a usually forbidden transition to the activated state of heterochromatin. Overall design: Refer to individual Series