This item is non-discoverable
Non-discoverable
MBD2 modulates heterochromatin architecture and composition
Loading...
Date
2024-09-09
Type
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Description
Heterochromatin (HC) is essential for nuclear integrity, genome stability, and gene regulation with pericentric heterochromatin (PCH) playing a key role. However, the mechanisms governing PCH compartmentalization remain poorly understood. Recent studies suggest that phase separation (PS) underlies the organization of various subnuclear compartments, including PCH. In this study, we integrated spatial proteomics, in vitro phase separation assays, and advanced PS prediction tools to identify and characterize candidate PS scaffold proteins involved in HC compartmentalization, particularly in PCH. We found that HC forms dynamic, phase-separated condensates that selectively enrich specific proteins. Approximately 1,000 HC PS-associated proteins were predicted, with around 250 predicted to possess scaffold PS properties. Further subcellular analysis identified 20 potential PS scaffold proteins in PCH, including Methyl-CpG binding domain protein 2 (MBD2). MBD2, a member of the NuRD complex, was shown to undergo LLPS via coiled-coil-mediated homooligomerization, forming liquid-like condensates that likely regulate PCH organization, as well as MBD-mC-mediated PPPS. This study advances our understanding of PCH compartmentalization by highlighting the role of MBD2 in PCH dynamics and provides new insights into the molecular mechanisms underlying nuclear architecture and opens avenues for future research into genome regulation and stability.
Citation
Endorsement
DFG Classification
Project(s)
Faculty
Collections
License
Except where otherwise noted, this license is described as CC-BY-NC 4.0 - Attribution-NonCommercial 4.0 International
Version History
You are currently viewing version no. 3 of the item. This is the most recent version.