PXD055626-1

PXD055626 is an original dataset announced via ProteomeXchange.

Title	MBD2 modulates heterochromatin architecture and composition
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.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_18:18:14.506.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	M. Cristina Cardoso
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-06 04:58:37	ID requested
⏵ 1	2025-12-28 18:18:15	announced

Zhang H, Ugur E, Hake C, Romero H, Arroyo M, Mahmoud M, Lermyte F, Leonhardt H, Cardoso MC, Heterochromatome wide analyses reveal MBD2 as a phase separation scaffold for heterochromatin compartmentalization and composition. Nucleic Acids Res, 53(22):(2025) [pubmed]

10.1093/nar/gkaf1380;

submitter keyword: Mice brain, DIA-MS, MBD2, pericentric heterochromatin, Alphafold Server, nuclear fractionation, PS prediction tools, phase separation

M Cristina Cardoso
contact affiliation	Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
contact email	cardoso@bio.tu-darmstadt.de
lab head
M. Cristina Cardoso
contact affiliation	Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
contact email	cardoso-lab@bio.tu-darmstadt.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD055626

PRIDE project URI

• PRIDE
  1. PXD055626
     1. Label: PRIDE project
     2. Name: MBD2 modulates heterochromatin architecture and composition