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MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid–liquid phase separation and restricted by DNA methylation

Zhang, Hui ; Romero, Hector ; Schmidt, Annika ; Gagova, Katalina ; Qin, Weihua ; Bertulat, Bianca ; Lehmkuhl, Anne ; Milden, Manuela ; Eck, Malte ; Meckel, Tobias ; Leonhardt, Heinrich ; Cardoso, M. Cristina (2022)
MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid–liquid phase separation and restricted by DNA methylation.
In: Nucleus (Austin, Tex.), 13 (1)
doi: 10.1080/19491034.2021.2024691
Article, Bibliographie

Abstract

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 and 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 system.

Item Type: Article
Erschienen: 2022
Creators: Zhang, Hui ; Romero, Hector ; Schmidt, Annika ; Gagova, Katalina ; Qin, Weihua ; Bertulat, Bianca ; Lehmkuhl, Anne ; Milden, Manuela ; Eck, Malte ; Meckel, Tobias ; Leonhardt, Heinrich ; Cardoso, M. Cristina
Type of entry: Bibliographie
Title: MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid–liquid phase separation and restricted by DNA methylation
Language: English
Date: December 2022
Journal or Publication Title: Nucleus (Austin, Tex.)
Volume of the journal: 13
Issue Number: 1
DOI: 10.1080/19491034.2021.2024691
Abstract:

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 and 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 system.

Identification Number: pmid:35156529
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 21 Feb 2022 12:44
Last Modified: 21 Feb 2022 12:44
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