A change in biophysical properties accompanies heterochromatin formation in mouse embryos

The majority of our genome is composed of repeated DNA sequences that assemble into heterochromatin, a highly compacted structure that constrains their mutational potential. How heterochromatin forms during development and how its structure is maintained are not fully understood. Here, we show that mouse heterochromatin phase-separates after fertilization, during the earliest stages of mammalian embryogenesis. Using high-resolution quantitative imaging and molecular biology approaches, we show that pericentromeric heterochromatin displays properties consistent with a liquid-like state at the two-cell stage, which change at the four-cell stage, when chromocenters mature and heterochromatin becomes silent. Disrupting the condensates results in altered transcript levels of pericentromeric heterochromatin, suggesting a functional role for phase separation in heterochromatin function. Thus, our work shows that mouse heterochromatin forms membrane-less compartments with biophysical properties that change during development and provides new insights into the self-organization of chromatin domains during mammalian embryogenesis. In this study, Guthmann et al. show that pericentromeric heterochromatin undergoes phase separation and transition during early embryonic development in mice. They further demonstrate that weak hydrophobic interactions and ATRX recruitment influence the biophysical properties of heterochromatin and chromocenter maturation, and their findings provide new insights into the self-organization of chromatin domains during mammalian embryogenesis.

Automated summary

In this study, Guthmann et al. demonstrate that pericentromeric heterochromatin undergoes phase separation and transition during early embryonic development in mice. They also show that weak hydrophobic interactions and ATRX recruitment influence the biophysical properties of heterochromatin and chromocenter maturation. These findings provide new insights into the self-organization of chromatin domains during mammalian embryogenesis.