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Guthmann, M. ; Qian, C.* ; Gialdini, I.* ; Nakatani, T. ; Ettinger, A. ; Schauer, T. ; Kukhtevich, I. ; Schneider, R. ; Lamb, D.C.* ; Burton, A. ; Torres-Padilla, M.E.

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

Genes Dev. 37, 336-350 (2023)
DOI PMC
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Embryo ; Heterochromatin ; Imaging; Phase-separation; Correlation Spectroscopy; Chromatin; Atrx; Organization; Proteins; Domain; Rna; Pluripotency; Localization
ISSN (print) / ISBN 0890-9369
e-ISSN 1549-5477
Journal Genes and Development
Quellenangaben Volume: 37, Issue: 7-8, Pages: 336-350 Article Number: , Supplement: ,
Publisher Cold Spring Harbor Laboratory Press
Publishing Place 1 Bungtown Rd, Cold Spring Harbor, Ny 11724 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Institute of Functional Epigenetics (IFE)
Grants
LMUinnovativ Initiative BioImaging Network (BIN)
Ludwig-Maximilian University, Munich via the Center for NanoScience (CeNS)
German Research Foundation)
Deutsche Forschungsgemeinschaft (DFG
German Research Foundation (DFG)
Helmholtz Association