Author:
Guthmann Manuel,Qian Chen,Gialdini Irene,Nakatani Tsunetoshi,Ettinger Andreas,Schauer Tamas,Kukhtevich Igor,Schneider Robert,Lamb Don C.,Burton Adam,Torres-Padilla Maria-Elena
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.
Funder
Helmholtz Association
German Research Foundation
Deutsche Forschungsgemeinschaft
Ludwig-Maximilian University
Munich via the Center for NanoScience
LMUinnovativ Initiative BioImaging Network
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
3 articles.
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