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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)
Publ. Version/Full Text 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
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
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Institiute 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