Academic Journal
MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid–liquid phase separation and restricted by DNA methylation
| Title: | MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid–liquid phase separation and restricted by DNA methylation |
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| Authors: | Hui Zhang, Hector Romero, Annika Schmidt, Katalina Gagova, Weihua Qin, Bianca Bertulat, Anne Lehmkuhl, Manuela Milden, Malte Eck, Tobias Meckel, Heinrich Leonhardt, M. Cristina Cardoso |
| Source: | Nucleus, Vol 13, Iss 1, Pp 1-34 (2022) |
| Publisher Information: | Taylor & Francis Group, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Genetics LCC:Cytology |
| Subject Terms: | dna methylation, heterochromatin, liquid-liquid phase separation, mecp2, protein–protein interaction, rett syndrome, single molecule tracking, Genetics, QH426-470, Cytology, QH573-671 |
| More Details: | Heterochromatin is the highly compacted form of chromatin with various condensation levels hallmarked by high DNA methylation. MeCP2 is mostly known as a DNA methylation reader but has also been reported as a heterochromatin organizer. Here, we combine liquid–liquid phase separation (LLPS) analysis and single-molecule tracking with quantification of local MeCP2 concentrations in vitro and in vivo to explore the mechanism of MeCP2-driven heterochromatin organization and dynamics. We show that MeCP2 alone forms liquid-like spherical droplets via multivalent electrostatic interactions and with isotropic mobility. Crowded environments and DNA promote MeCP2 LLPS and slow down MeCP2 mobility. DNA methylation, however, restricts the growth of heterochromatin compartments correlating with immobilization of MeCP2. Furthermore, MeCP2 self-interaction is required for LLPS and is disrupted by Rett syndrome mutations. In summary, we are able to model the heterochromatin compartmentalization as well as MeCP2 concentration and heterogeneous motion in the minimal in vitro system. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1949-1034 1949-1042 19491034 |
| Relation: | https://doaj.org/toc/1949-1034; https://doaj.org/toc/1949-1042 |
| DOI: | 10.1080/19491034.2021.2024691 |
| Access URL: | https://doaj.org/article/f32134fb8d744d22b07daf1e94f6c84b |
| Accession Number: | edsdoj.f32134fb8d744d22b07daf1e94f6c84b |
| Database: | Directory of Open Access Journals |
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| ISSN: | 19491034 19491042 |
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| DOI: | 10.1080/19491034.2021.2024691 |
| Published in: | Nucleus |
| Language: | English |