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Publication : A change in biophysical properties accompanies heterochromatin formation in mouse embryos.

First Author  Guthmann M Year  2023
Journal  Genes Dev Volume  37
Issue  7-8 Pages  336-350
PubMed ID  37072228 Mgi Jnum  J:341518
Mgi Id  MGI:7538788 Doi  10.1101/gad.350353.122
Citation  Guthmann M, et al. (2023) A change in biophysical properties accompanies heterochromatin formation in mouse embryos. Genes Dev 37(7-8):336-350
abstractText  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.
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