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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Embryo ; Heterochromatin ; Imaging; Phase-separation; Correlation Spectroscopy; Chromatin; Atrx; Organization; Proteins; Domain; Rna; Pluripotency; Localization
ISSN (print) / ISBN 0890-9369
e-ISSN 1549-5477
Zeitschrift Genes and Development
Quellenangaben Band: 37, Heft: 7-8, Seiten: 336-350 Artikelnummer: , Supplement: ,
Verlag Cold Spring Harbor Laboratory Press
Verlagsort 1 Bungtown Rd, Cold Spring Harbor, Ny 11724 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)
Institute of Functional Epigenetics (IFE)
Förderungen
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