A change in biophysical properties accompanies heterochromatin formation in mouse embryos
- Manuel Guthmann1,
- Chen Qian2,
- Irene Gialdini2,
- Tsunetoshi Nakatani1,
- Andreas Ettinger1,
- Tamas Schauer1,
- Igor Kukhtevich3,
- Robert Schneider3,
- Don C. Lamb2,
- Adam Burton1 and
- Maria-Elena Torres-Padilla1,4
- 1Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, D-81377 München, Germany;
- 2Department of Chemistry, Center for NanoScience (CeNS), Ludwig Maximilians-Universität München, 81377 München, Germany;
- 3Institute of Functional Epigenetics (IFE), Helmholtz Zentrum München, D-85764 Neuherberg, Germany;
- 4Faculty of Biology, Ludwig-Maximilians Universität, München, 82152 Planegg, Germany
- Corresponding author: torres-padilla{at}helmholtz-muenchen.de
Abstract
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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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.350353.122.
- Received December 13, 2022.
- Accepted March 31, 2023.
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