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

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dc.contributor.author Zhang, Hui
dc.contributor.author Romero, Hector
dc.contributor.author Schmidt, Annika
dc.contributor.author Gagova, Katalina
dc.contributor.author Qin, Weihua
dc.contributor.author Bertulat, Bianca
dc.contributor.author Lehmkuhl, Anne
dc.contributor.author Milden, Manuela
dc.contributor.author Eck, Malte
dc.contributor.author Meckel, Tobias
dc.contributor.author Leonhardt, Heinrich
dc.contributor.author Cardoso, M. Cristina
dc.date.accessioned 2021-11-09T09:08:12Z
dc.date.available 2021-11-09T09:08:12Z
dc.date.created 2021
dc.date.issued 2021-11-09
dc.description 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. de_DE
dc.description.version For review de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/3100
dc.identifier.uri https://doi.org/10.48328/tudatalib-672
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject DNA methylation de_DE
dc.subject heterochromatin de_DE
dc.subject liquid-liquid phase separation de_DE
dc.subject MeCP2 de_DE
dc.subject protein-protein interaction de_DE
dc.subject Rett syndrome de_DE
dc.subject single-molecule tracking de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid-liquid phase separation and restricted by DNA methylation de_DE
dc.type Software de_DE
dc.type Image de_DE
dc.type Model de_DE
dcterms.accessRights openAccess
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person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
person.identifier.orcid #PLACEHOLDER_PARENT_METADATA_VALUE#
tuda.history.classification Version=2020-2024;201-03 Zellbiologie
tuda.project DFG | CA198/10-1 | Interaktion zwischen
tuda.project DFG | CA198/16-1 | Rölle und Regulation
tuda.unit TUDa

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