A change in biophysical properties accompanies heterochromatin formation in mouse embryos
Open Access
- 1 April 2023
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 37 (7-8), 336-350
- https://doi.org/10.1101/gad.350353.122
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.Keywords
Funding Information
- Helmholtz Association
- German Research Foundation (213249687, SFB 1064)
- Deutsche Forschungsgemeinschaft (201269156, SFB 1032 Project B03)
- Ludwig-Maximilian University
- Munich via the Center for NanoScience
- LMUinnovativ Initiative BioImaging Network
This publication has 64 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndromeNature Structural & Molecular Biology, 2011
- Histone H4K20me3 and HP1α are late heterochromatin markers in development, but present in undifferentiated embryonic stem cellsJournal of Cell Science, 2011
- Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytesProceedings of the National Academy of Sciences of the United States of America, 2011
- Epigenetic reprogramming and development: a unique heterochromatin organization in the preimplantation mouse embryoBriefings in Functional Genomics, 2010
- A Strand-Specific Burst in Transcription of Pericentric Satellites Is Required for Chromocenter Formation and Early Mouse DevelopmentDevelopmental Cell, 2010
- Loss of Maternal ATRX Results in Centromere Instability and Aneuploidy in the Mammalian Oocyte and Pre-Implantation EmbryoPLoS Genetics, 2010
- The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3Genes & Development, 2010
- Raster image correlation spectroscopy (RICS) for measuring fast protein dynamics and concentrations with a commercial laser scanning confocal microscopeJournal of Microscopy, 2007
- ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytesDevelopmental Biology, 2004